This study aims to describe and compare the distribution of bioactive compounds, the fatty acids profiles, and the TEAC hydrophilic and lipophilic antioxidant activities in different fruit fractions (pulp, peel, and kernel) of two mango cultivars (Tommy Atkins and Keitt). All fractions are sources of health-promoting bioactive compounds. Regardless of cultivars, pulp had the highest content of phytosterols (~150 mg/100 g dw), peels ranked first for pentaciclic triterpenes (from 14.2 to 17.7 mg/100 g dw), tocopherols, carotenoids, and chlorophylls, and kernels for phenolic compounds (from 421.6 to 1464.8 mg/100 g dw), flavonoids, condensed tannins, as well as hydrophilic and lipophilic antioxidant activities. Differences between the two cultivars were evidenced for ascorbic acid, which showed the highest levels in the peels and kernels of Keitt and Tommy Atkins fruits, respectively. Similarly, the concentration of dehydroascorbic acid was higher in the pulp of Tommy Atkins than Keitt. The highest percentage of saturated fatty acids was observed in pulp (~42%) and kernels (~50%), monounsaturated fatty acids in kernels (up to 41%), and polyunsaturated fatty acids in peels (up to 52%). Our results add information to the current knowledge on nutraceuticals’ distribution in different fractions of mango fruit, supporting its consumption as a healthy fruit and suggesting the great potential value of peels and kernels as sources of novel ingredients. Indeed, mango by-products generated during agronomic-to-industrial processing not only causes a significant environmental impact, but economic losses too. In this scenario, boosting research on conventional recovery methods offers eco-friendly solutions. However, green, novel biorefinery technologies may offer eco-friendly and profitable solutions, allowing the recovery of several more profitable by-products, sustaining their continuous growth since many bioactive compounds can be recovered from mango by-products that are potentially useful in the design of innovative nutraceutical, cosmeceutical, and pharmaceutical formulations.