The methanolic extract of dried fruit pulp of Citrullus colocyn this (Cucurbitaceae) has been studied with respect to antimicrobial and toxicological properties. The antimicrobial profile was investigated against thirty bacterial isolates (10 Gram +ve and 20 Gram-ve) and five fungal species. None of the bacterial or fungal culture used in the study showed sensitivity against the extract. Acute toxicity studies carried out in Albino mice NMRI indicated the highly toxic nature of the colocynth. A very significant decrease in body weight of test animals was noted at P<0.05. The LD(50) was calculated as 1000mg/kg body weight. Within four days of experimentation mortality was 100%. Histopathological studies confirmed the toxic nature of extract. Gross changes in histology of Heart, Liver and Kidneys were noted. Section of spleen did not exhibit any abnormality.