The aim of this study was to improve the extraction yield of polyphenols from mango seed kernel by solvent extraction. Seven organic solvents were tested to identify the best extraction efficiency, and a ternary solvent mixture of Methanol-Acetone-Water (54: 23:23), developed using the mixture design methodology, allowed to extract the maximum amount of polyphenols with maximum antioxidant activity. The solvent mixture developed was then applied to polyphenols extraction from kernels of 11 mango varieties from the savannah region of Cameroon, and High Pressure Thin Layer Chromatography (HPTLC) used to identify the phenolic compounds present in the extracts. The total polyphenols contents (TPC), flavonoids and Total Reducing Power (TRP) of mango kernels were respectively in the range of 93.38 - 121.01 mg Gallic Acid Equivalent/ g DW, 12.64 - 16.26 mg Catechin Equivalent/g DW and 95.42 - 113.97 mg Ascorbic Acid Equivalent/g DW. Chlorogenic acid, Mangiferin, Gallic acid and Methyl gallate are highly suspected as component molecules of polyphenols from mango seed kernel.