In this study, microwave extraction (ME) of pectic polysaccharides (M‐CPPs) from cantaloupe peels (CPs) is optimized using response surface methodology (RSM) with a Box–Behnken design (BBD). The optimum ME parameters are liquid–solid ratio 26.04 mL g−1, microwave power 543.04 W, irradiation time 6.38 min, and pH 1.5. Compared heat reflux extraction polysaccharides (H‐CPPs), the yield, the contents of neutral sugars (TSC), uronic acids (UAC), total flavonoids (TFC), total phenolics (TPC), sulfate groups (SGC) of M‐CPPs increased by 156.06%, 15.33%, 7.27%, 1019.05%, 1.75%, and 57.89%, but the molecular weight (Mw) and degree of esterification (DE) reduced by 29.08% and 24.81%, respectively. M‐CPPs exhibit superior antioxidant and hypoglycemic activities than H‐CPPs, which may be attributed to its higher UAC, TFC and SGC, lower Mw, and DE. There is almost no change in the monosaccharide types of isolated polysaccharides, only a change in molar ratio. Results proved that ME is an efficient technique for the extraction and modification of pectic polysaccharides (CPPs) from CPs with high yield, strong antioxidant, and hypoglycemic activities for applications in medical and food industries.