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Cancer is one of the most life-threatening diseases and widespread in both developed and developing countries. Accumulation of genetic alterations is main etiology for cancer developments. Many of the Cucurbitaceae plants possess antitumor activity traditionally. Methanolic extract of Lagenaria siceraria Standley Fruit was tested for their antimutagenic potential. The extract of plant exhibited varying level of antimutagenicity. Ames test was used in the current study to evaluate antimutagenic activity in TA98 and TA100 strains of Salmonella typhimurium using direct (Sodium azide) acting mutagens. Results of the study showed significant antimutagenicity against mutagen in TA98 and TA100 strains. The antimutagenicity of the extract observed in the present study implies chemopreventive pharmacological importance of Lagenaria siceraria Standley Fruit and encourages its use as a functional food.