Macrotyloma uniflorum (Lam.) Verdc., commonly known as horse gram, is an important source of nutrients in human but its nutrients are lost by the post-harvest infestation of Callosobruchus chinensis (L.) (Coleoptera: Chrysomelidae: Bruchinae). The biology, life table parameters and resistance of C. chinensis on four horse gram cultivars (AK 21, ANK Black, Paiyur 2 and Urmi) were evaluated. Nutrients (total proteins, carbohydrates, amino acids, lipids and nitrogen) and antinutrients (total phenols, tannins and flavonols) of these cultivars were estimated. Further, insect embryogenesis and several key digestive enzymes of C. chinensis larvae were studied on these four cultivars. Callosobruchus chinensis showed longer development time, lower fecundity and lower survival rate on Urmi due to lower amounts of nutrients and higher amounts of antinutrients than other cultivars. Adult emergence also decreased on Urmi. Based on growth index, Urmi is moderately resistant. The relative growth rate of C. chinensis was lowest on Urmi. The rm, R0 and λ of C. chinensis were lowest in Urmi, suggesting the lower increase of C. chinensis population on Urmi than other three cultivars. Larval post-embryonic development (cellular blastoderm formation, germ band extension or retraction, segmentation of embryo and dorsal closure) was delayed on Urmi than other cultivars. α-Amylase, cysteine protease, α-glucosidase and lipase enzyme activities were reduced in larvae developed on Urmi than other cultivars. Therefore, we could recommend the use of moderately resistant Urmi cultivar as a way to lessen C. chinensis infestation, and suggesting resistance mechanism is due to reduced activities of key digestive enzymes.