Medicinal plants are being popular these days to cure diseases due to rapid increase in the rate of infectious diseases day by day and their less side effects over synthetic antibiotics. In the present study two medicinally important plants of family cucurbitaceae vis. Luffa cylindrica Linn. and Citrullus colocynthis Linn. Leaf, stem and calli phytochemical extracts viz. alkaloids, flavonoids and sterols were evaluated against some pathogenic strains of bacteria and fungi viz. Staphylococcus epidermis (MTCC 3615), Micromona spora (MTCC 3296), Fusarium culmorum (MTCC349), Alternaria solani (MTCC 2101), Penicillium chrysogenum (MTCC 161). The antibacterial and antifungal activities were performed by Disc diffusion method. The  on the basis of inhibition zone(IZ) and minimum inhibitory concentration (MIC).Among all the extracts sterol extracts of both the plant species showed highest antimicrobial activity. Results obtained in the present study indicate Luffa cylindrical Linn. and Citrullus colocynthis Linn. Leaf, stem and calli phytochemical extracts viz. alkaloids, flavonoids and sterols possesses antimicrobial properties that can be exploited for future natural plant based antimicrobial agents.