Melon fly is one of the serious pest worldwide infesting cucurbitaceous fruits inducing considerable damage resulting insufficient growth and economical loss. It is known that the susceptibility and resistance against melon fly infestation among cucurbittae fruits varies considerably. Henceforth, present study attempts to understand the cellular antioxidants potential and Phenyl Proponoid Pathway (PPP) enzyme expression among different cucurbittae fruits during infestation to compare susceptibility and resistance. This experiment conduct was healthy and melon fly infected cucurbittae fruits (Snake guard, bitter guard and bottle gourd) were selected and analyzed for phytoconstituents. In vitro antioxidant potential and expression of antioxidant enzymes and larvicidal activity in healthy and infected were compared. The PPP pathway enzyme level and expressions were also compared in healthy and infected fruit samples. Melon fly infestation considerably increases the contents of phenolic and flavanoids components in cucurbittae fruits compared to their healthy counterparts. Antioxidant enzymes expression found high in infected tissue samples as compared to healthy and apparent healthy. These observations indicate melon fly infestation induces cellular oxidative damage which was defended by increased antioxidant potential in infected fruits. The PPP pathway enzymes ((Phenylalanine Ammonia-Lyase (PAL) and Tyrosine Ammonia-Lyase (TAL), Cinnamyl Alcohol Dehydrogenase (CAD)), were also seen increased in expression by infected tissues which define the increased lignin synthesis at infestation site to provide resistance. Present comparative observations conclude bottle guard is more resistant whereas snake guard and bitter guard are susceptible for melon fly infestation. The resistance provided is linked with increased antioxidant potential and PPP pathway enzyme expression involved in lignin synthesis which oppose cellular damage and melon fly development and infection. Importance role of latex lectin is defense mechanism against insect, pathogens. There larvae activity of latex lectin has been importance documentation used as naturally occurs larvae with pest.