In this study, silver nanoparticles were synthesized usingCucumis meloL. leaf extract via a green synthesis approach and their potential against diabetes and coccidiosis was tested under in vitro conditions. The phytochemical components in the leaf extract reacted with silver nitrate in solution and yieldedC. melo-silver nanoparticles (Cm-AgNPs). The synthesis of AgNPs was confirmed via UV–visible spectroscopy by obtaining a peak at 440 nm. The nanoparticles were characterized by their morphology, crystallinity, and the presence of functional groups. In vitro α-amylase and α-glucosidase inhibition assays were carried out at different concentrations in the range of 20 to 100 μg/mL ofCm-AgNPs. TheCm-AgNPs exhibited enzyme inhibitory activity in a concentration-dependent manner. As the concentration ofCm-AgNPs increased the inhibitory activities were also increased linearly and the highest inhibition was observed at 100 μg/mL. The effectiveness ofCm-AgNPs againstEimeria tenallawas assessed by an in vitro 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay using Madin–Darby bovine kidney (MDBK) cell lines. The results revealed that the viability of the oocysts and further sporulation were decreased with the increased concentration ofCm-AgNPs. The AgNPs synthesized from theC. meloleaf extract have shown promising potential against diabetes and coccidiosis, and they could be used in biomedical applications.