The light mango or “Ma-Muang Bao” (Mangifere indica L. var.) is a native mango species originating from Malaysia and southern Thailand. The whole Ma-Muang Bao fruit, except peels, is popular as both a raw and ripe fruit for consumption, as well as being used in various processed food products. This study aims to transform the peel of a specific mango variety, which is a byproduct of the agro-industrial sweet, pickled mangoes industry, into a valuable bioactive ingredient for healthcare products. This is achieved through the establishment of a standardized mangiferin-rich mango peel extract (SMPE). Employing the Box–Behnken design (BBD) within the framework of response surface methodology (RSM), an optimal microwave-assisted extraction procedure was developed. A total of 27 experiments, each with four independent variables, including solvent ratio, extraction power, extraction time, and ethanol (EtOH) ratio, were conducted to optimize the extraction method in terms of mangiferin content and extraction yield. The optimized extraction conditions encompassed a solvent ratio of 120 mL EtOH/100 g sample, an extraction power of 450 W, an extraction time of approximately 4.3 min, and an EtOH ratio of 69.44% (EtOH in water). Small-scale extractions were carried out using the following specified parameters: solvent ratio of 120 mL, extraction power of 450 W, extraction time of 4 min, and EtOH ratio of 70% EtOH. These extractions yielded an extract with a mangiferin content of 27.24 ± 2.05 mg/g and an extraction yield of 3.71 ± 0.17% w/w. Notably, these outcomes were better from the mangiferin content of 19.62 mg/g and a yield of fresh peel of 5.61% estimated through BBD analysis. Furthermore, a pilot-scale extraction was performed using 7 kg of fresh mango peel and 70% EtOH (8.4 L) for 4 min, resulting in an extract with a mangiferin content of 51.85 ± 0.35 mg/g and a fresh peel yield of 4.35% w/w. This method emerges as the most suitable for mango peel extraction and forms the basis of the SMPE. The results from biological activities highlight the potential use of SMPE as the active ingredient for cosmeceutical or healthcare products for wound-healing and skin-brightening agents. Additionally, the knowledge from this study presents an alternative approach to various plant sources and sustainable extraction methods for the herbal extract industry.