Epiphyllum oxypetalum (E. oxypetalum) is traditionally used to cure liver infections, for wound healing, and to alleviate viral–related diseases. However, as the alcohol and aqueous solvents have low total phenolic and flavonoid content (TPC and TFC), antioxidant, and antibacterial capabilities, a different polarity would be more suitable. Thus, this study aimed to evaluate the methanolic extract of E. oxypetalum leaf. The chemical constituents were identified through TPC and TFC, as well as GC–MS analysis. The methanolic extract of E. oxypetalum leaf was evaluated for antimicrobial properties against five bacterial strains - Klebsiella pneumoniae, Staphylococcus aureus, Escherichia coli, Staphylococcus epidermidis, and a fungal strain of Candida albicans using the disc diffusion method. The antioxidant activity of the methanolic extract of E. oxypetalum leaf was also assessed using DPPH assay. The highest values of the TPC and TFC of the methanolic extract of E. oxypetalum leaf were 179.86 ± 0.17 mg GAE/g and 75.07 ± 0.17 mg QE/g, respectively. The GC–MS had 27 m/z peaks, indicating the presence of various bioactive compounds including phenolic compounds and fatty acids. In the antimicrobial study, the zone of inhibition (ZOI) was between 2.8–3.5 mm for antibacterial activity and there was also a significant antifungal activity of 1.8 mm against Candida albicans. The IC50 DPPH assay value of methanolic extract of E. oxypetalum leaf was 14 µg/ml, indicating high antioxidant properties. This study provides evidence that the methanolic extract of E. oxypetalum leaf possesses significant antioxidant and antimicrobial properties which could be attributed to its diverse chemical constituents. These findings suggest the potential of E. oxypetalum leaf as a natural source of medicine, antimicrobial, and antioxidant properties.