Abstract: To optimize the ultrasound-assisted extraction of phenolic compounds from the fruits and persistent calyces of two Physalis cultivars and clarify their in vitro antioxidant activity, hypoglycemic enzyme inhibitory activity and gastrointestinal digestive stability, mature fruits and calyces of Alkekengi officinarum（red-fruited）and Physalis peruviana（yellow-fruited）were used as materials. The extraction process was optimized by single-factor experiments combined with orthogonal array design. The biological activities were evaluated via DPPH, ABTS assays, α-amylase and α-glucosidase inhibition tests, and in vitro digestive stability was analyzed based on the standardized INFOGEST model.The results showed that the total phenolic content of red-fruited calyces was the highest（62.25 mg GAE·g⁻¹). The optimal extraction conditions were as follows: 70% methanol for red fruits, yellow fruits and yellow-fruited calyces, 60% methanol for red-fruited calyces, solid-to-liquid ratio of 1∶20 g·mL⁻¹, and ultrasonic treatment for 20–30 min. Solid-to-liquid ratio was the dominant factor affecting extraction efficiency. All phenolic extracts exhibited favorable in vitro bioactivities: red-fruited calyces showed the strongest ABTS⁺ scavenging activity（IC₅₀ = 0.375 mg·mL⁻¹), yellow fruits had the strongest DPPH· scavenging activity（IC₅₀ = 0.302 mg·mL⁻¹), and red fruits exerted the most significant inhibition on α-glucosidase（IC₅₀ = 0.472 mg·mL⁻¹）and α-amylase（IC₅₀ = 0.0677 mg·mL⁻¹). After simulated digestion, the activity retention rate in the gastric phase was significantly higher than that in the intestinal phase, and all samples maintained favorable bioactivity after complete gastrointestinal digestion.This study provides the first evidence of the synergistic effect of fruit color and persistent calyx on the functional activity of Physalis, which offers a scientific basis for the high-value utilization of Physalis calyx by-products and the development of natural glycemic-control functional foods.