Despite the widespread use of Luffa cylindrica in traditional medicine, there is limited scientific validation of its safety profile and phytochemical composition, raising concerns about its unregulated therapeutic use. Both the qualitative and quantitative phytochemical analysis of L. cylindrica leaf extracts using various solvents revealed the presence of several bioactive compounds, including cardiac glycosides, terpenoids, saponin glycosides, tannins, flavonoids, carbohydrates, and cardenolides, all of which are known for their diverse pharmacological activities UV–Vis double-beam spectrophotometer (for absorbance measurements) was used to demine the quantitative. Solvent fractionation facilitated the isolation of these compounds based on polarity and solubility. Elemental analysis further indicated the presence of essential and trace minerals such as calcium (941.7 mg/kg), magnesium (234.6 mg/kg), potassium (928.4 mg/kg), sodium (858.1 mg/kg), iron, zinc, and copper, which are vital for various biological and metabolic processes. Acute toxicity evaluation demonstrated moderate toxicity at a high dose (4000 mg/kg), suggesting that while the extract may be relatively safe at lower concentrations, caution is warranted at higher doses. Therefore, although L. cylindrica holds significant therapeutic potential, its use should be approached with careful consideration of dosage and treatment duration to ensure safety and avoid adverse effects.