A comprehensive study was conducted during the kharif seasons of 2019-20 and 2020-21 to optimize the saline irrigation water with amendments such as gypsum, farmyard manure (FYM), and vermicompost on the performance of the cucurbitaceous crop Kachri (Cucumis callosus). The research was focused on both crop yield and the phytochemical composition, including antioxidant properties of Kachri crop variety AHK-119. The results indicated that the application of saline irrigation water with amendments significantly enhanced Kachri crop yield and yield response compared to the control. The highest yield was recorded with the treatment of Gypsum @5 ton/ha + 4.0 ECIW, yielding 85.00 q/ha, followed by Vermicompost @10 ton/ha + 4.0 ECIW (78.50 q/ha) and FYM @15 ton/ha + 4.0 ECIW (76.23 q/ha). The control treatment with 4.0 ECIW yielded 52.23 q/ha. Under lower salinity (0.5 ECIW), the highest yield was achieved with FYM @15 ton/ha + 0.5 ECIW (89.83 q/ha), followed by Vermicompost @10 ton/ha + 0.5 ECIW (84.67 q/ha) and Gypsum @5 ton/ha + 0.5 ECIW (76.45 q/ha). The highest dry matter percentages of 12.25% and 12.79% were observed with FYM at 15 ton/ha, regardless of saline water conditions. Significant improvements in leaf area (52.97 cm²), leaf area index (0.75), and total soluble solids (TSS) (4.09 °Brix) were recorded with Gypsum at 4 ton/ha + 4 ECIW. The maximum yield response was observed with FYM at 15 ton/ha + 0.5 ECIW (68.8%), followed by Vermicompost at 10 ton/ha + 0.5 ECIW (63.7%) and Gypsum at 5 ton/ha + 0.5 ECIW (55.0%). Under 4.0 ECIW, the highest yield response was recorded with Gypsum at 5 ton/ha + 4.0 ECIW (49.0%), followed by Vermicompost at 10 ton/ha + 4.0 ECIW (45.83%) and FYM at 15 ton/ha + 4.0 ECIW (41.66%). Phytochemical analysis revealed higher total phenols, flavonoids, and antioxidant activity under 0.5 ECIW, suggesting that Kachri fruits grown under these conditions possess enhanced antioxidant properties. This study demonstrates that Kachri fruits, particularly under optimized irrigation and amendment treatments, offer significant potential for applications in food, nutraceuticals, and agriculture. The findings provide valuable comprehension into enhancing both the yield and bioactive properties of Kachri, contributing to sustainable agricultural practices in arid regions.