Lagenaria siceraria (Bottle gourd) was described in ancient Indian text ayurveda for varied health benefits. We have previously reported that the crude latex sap from L. siceraria with potent lectin activity significantly regresses the tumor progression by targeting angiogenesis and inducing cell death. In this present investigation the semipurified latex lectins from L. siceraria latex were investigated for antiproliferative activity in mice models. The L. siceraria latex sap agglutinin (LSA) were isolated by ammonium sulphate precipitation. LSA agglutinated trypsinizeed chick and human erythrocytes irrespective of blood type. Heamagglutination was inhibited by glycoproteins comprising of complex oligosaccharides and not with simple carbohydrates. LSA exerted significant cytotoxicity towards murine DLA cells in-vitro. Further the in-vivo anti-proliferative of LSA elucidated a clear regression of Dalton’s lymphoma ascites tumor in mice. Hispathological and immunohistochemistry studies inferred LSA abrogated microvessel density (MVD) leading to the tumor inhibition and prolonged survival. This is further evident from the decreased VEGF levels in ascites. In conclusion, this study reports that the semipurified LSA exerts potent antiproliferative activity activity targeting tumor angiogenesis. This investigation highlighting the bioactivity of semipurified LSA for the first time, has potential therapeutic implications for malignant pathologies.