Peptic ulcer disease (PUD) constitutes one of the most persistent gastroenterological disorders worldwide, with significant morbidity linked to gastric acid hypersecretion, oxidative stress, Helicobacter pylori infection, NSAID exposure, and compromised mucosal defensive integrity. Although numerous pharmacological options—including proton pump inhibitors, H? antagonists, prostaglandin analogues, and antibiotics—are available, their long-term utility remains constrained by adverse effects, recurrence, microbial resistance, and inadequate mucosal restitution. This has catalysed renewed scientific interest in botanicals with multifaceted gastroprotective actions. Trichosanthes dioica (Roxb.) leaves represent a phytochemically dense cucurbitaceous plant component historically utilized in Indian ethnomedicine for gastrointestinal, metabolic, hepatic, and inflammatory conditions. However, compared to fruits and roots, the leaves remain considerably under-investigated despite their rich flavonoid, phenolic, triterpenoid, saponin, and cucurbitacin profile. This review undertakes a rigorous pharmacognostic, phytochemical, mechanistic, and experimental examination of the gastroprotective potential of T. dioica leaves. Mechanistic emphasis is placed on antioxidant reinforcement, modulation of oxidative microenvironment, regulation of prostaglandin-mediated defence, inhibition of parietal proton pump activity, suppression of inflammatory cascades, stabilization of mast cells, modulation of nitric oxide bioavailability, and acceleration of epithelial restitution. The article aligns with the structural, stylistic, and referencing standards of the American Journal of PharmTech Research (AJPTR). The cumulative evidence demonstrates that T. dioica leaves exhibit significant gastroprotective effects, warranting their consideration as a promising phytopharmaceutical candidate for future antiulcer therapeutics.