Peptic ulcer disease (PUD) is a common gastrointestinal disorder marked by lesions and damage to the mucosal lining of the stomach and duodenum [1], [2], [3], [4], [5]. This mucosal injury may extend to the muscularis mucosa and reach deeper layers [6]. The most important etiologies of peptic ulcers include H. pylori infection and the use of nonsteroidal anti-inflammatory drugs (NSAIDs) which contribute to ulcer formation through mechanisms such as increased acid secretion, mucosal damage, and disruption of the mucosal defense barrier [3], [4], [7], [8], [9], [10], [11], [12]. Clinical manifestations can range from being asymptomatic to abdominal pain, dyspepsia, epigastric discomfort, feeling of fullness in the upper abdomen, early satiety, nausea, intermittent vomiting, and sensitivity to fatty foods [13], [14], [15]. Additionally, peptic ulcer complications such as perforation, hemorrhage, obstruction, and penetration are associated with higher rates of mortality and morbidity (often due to multi-organ failure and cardiopulmonary complications [5], [16], [17], [18], [19], [20], [21]. PUD associated with H. pylori infection is also linked to a higher risk of gastrointestinal cancers such as gastric adenocarcinoma, mucosa-associated lymphoid tissue lymphoma, and pancreatic cancer [9], [22], [23], [24], [25], [26], [27].

The prevalence of PUD in the general population is estimated at one case per 1000 individuals a year, and it affects millions globally [28], [29], [30]. It also has a prevalence of 5–10 % in the general population and significantly affects quality of life and health care costs [2], [3], [28], [31].

The primary treatments for PUD include proton pump inhibitors (PPIs) and antibiotics aimed at eradicating H. pylori [32]. However, both treatment options are associated with numerous side effects, significant medication resistance, and potential drug interactions, often leading to disease recurrence or treatment failure [1], [5], [9], [31], [33], [34], [35], [36], [37]. Gastrointestinal intolerance to these medications can reduce patient adherence to prescribed regimens. Although proton pump inhibitors (PPIs) are recognized for their efficacy and safety profiles, their long-term use raises significant concerns. Prolonged use of PPIs has been linked to an increased risk of Clostridium difficile infection, acute interstitial nephritis, microscopic colitis, hypergastrinemia, atrophic gastritis, malabsorption, colonization by multidrug resistant organisms, and a higher likelihood of developing inflammatory bowel disease [38], [39], [40], [41], [42], [43], [44], [45], [46]. Also extended use of PPIs can lead to electrolyte imbalances, including hypomagnesemia and hypocalcemia, potentially causing symptoms such as heart rhythm abnormalities, tetany, and seizures [39], [45]. Moreover, the eradication of H. pylori requires a multidrug regimen, typically involving at least two antibiotics [36], [47], [48], [49], [50]. Despite significant advancements, this disease remains a major clinical challenge, largely driven by the increasing use of non-steroidal anti-inflammatory drugs (NSAIDs) and low-dose aspirin [15].

Complementary treatments such as herbal medicines are considered beneficial for managing stomach disorders [3], [51], [52], [53], [54]. This is due to their accessibility, lower side effects, greater environmental compatibility, positive treatment outcomes, and improved quality of life [1], [6], [8], [25], [30]. Licorice is an effective plant for gastric ulcers, with a therapeutic history spanning thousands of years. It has been used to manage gastric ulcers, infections, abdominal discomfort, and asthma [55]. Studies have shown that liquorice extract is effective in preventing the adhesion of Helicobacter pylori to the gastric mucosa. This mechanism is crucial, as it not only inhibits the establishment of H. pylori infection but also plays a preventive role in the development of gastric ulcers. By preventing bacterial colonization, liquorice extract helps maintain the integrity of the gastric lining and reduces the risk of ulcer formation, thereby contributing to overall gastrointestinal health. The anti-ulcer effects of liquorice root can be attributed to its ability to inhibit stomach acid secretion, enhance mucosal defense mechanisms, increase the production of protective mucus, stabilize surface epithelial cells, and promote prostaglandin synthesis [55], [57], [58], [59], [60]. These properties suggest that liquorice root has potential as a natural remedy for gastric ulcers, warranting further investigation into its mechanisms of action and therapeutic efficacy.

Carbenoxolone, a licorice derivative, has shown efficacy in treating stomach ulcers as well [56]. Its preventive effects for wound prophylaxis in high-risk individuals along with its anti-ulcer properties have been supported through anti-inflammatory and antibacterial pathways [57], [58], [59], [60]. Since 1948, numerous studies have explored the clinical impact of carbenoxolone on peptic ulcer healing. Despite its notable benefits, carbenoxolone has also been linked to adverse effects, including fluid retention and edema, elevated blood pressure, and electrolyte imbalance, which explains why clinical research has focused on developing a licorice derivative with fewer side effects. Deglycyrrhizinated licorice (DGL) was created by reducing glycyrrhizic acid from licorice hence eliminating the negative effects associated with carbenoxolone and has apparently proven beneficial in alleviating PUD symptoms. One such therapeutic product is Caved-S, a DGL complex that contains licorice from which 3 % of the glycyrrhizinic acid has been removed, in addition to antacids and powdered frangula bark [56]. Numerous clinical studies were conducted on DGL and Cave-s forms until 2000, with different results. Since 2000, most clinical trials investigating licorice have focused on its anti-H pylori properties in the treatment of PUD [61], [62], [63]. Other studies specifically addressing peptic ulcers have often used animal models [55], [57], [58], [59], [60].

Licorice root, with its multiple mechanisms of action, represents a promising avenue for developing adjunctive treatments that could reduce side effects and enhance healing in peptic ulcers. Although studies on the effects of licorice in managing peptic ulcers have been conducted for years, there is a lack of scientifically validated data regarding its efficacy, optimal dosages, and safety profiles. Given that studies on the effects of licorice on peptic ulcers, particularly about Helicobacter pylori, are still ongoing, this study aims to conduct a systematic review and meta-analysis to assess the efficacy of licorice in managing peptic ulcers. To achieve this objective, we examined clinical symptoms, along with radiological and endoscopic findings, in randomized controlled trials.