Fruit by-products are a sustainable and cost-effective alternative to traditional grain feed for livestock. One of the most important by-products is mango seed kernel (MSK), which can be used as a valuable energy source for feeding growing calves in the tropical and subtropical productive regions of the world. This study investigated the effect of replacing corn grains (CGs) with MSK on intake, nutrient digestibility, blood metabolites and rumen parameters. Eighteen growing male Friesian calves (200 ± 6.55 kg of body weight and 9-11 months old) were randomly assigned to three treatment groups. Three concentrate feed mixtures were formulated such that MSK replaced CG at 0%, 25% and 50%. Dry matter intake was unaffected, whereas dry matter, organic matter and fibre digestibility increased linearly (p < 0.05) with increased inclusion of MSK. Ruminal pH (p = 0.053) and total volatile fatty acid (VFA) concentration (p = 0.041) increased linearly. There was a linear decrease in cholesterol (p = 0.029) and AST (p = 0.028) levels in the blood of calves. In conclusion, this study demonstrated the positive effect of replacing 50% of CG with MSK on rumen parameters, including a higher ruminal pH and total VFA concentration, alongside higher nutrient digestibility. The dietary inclusion of mango seed can serve as a valuable and sustainable dietary component for growing calves.