Curcumin is known for its various therapeutic properties like anti-inflammatory, antioxidant, anticancer, however, its oral use is restricted due to its low solubility and dissolution rate in alkaline pH. In this study co-amorphous mixture of curcumin–ascorbic acid (CU:AA) of different molar ratios was prepared using the ball milling method. The solubility and characterization of the mixture were studied using FTIR, DSC, and XRD study. Mixture (1:0.50) molar ratio showed the highest solubility and was formulated in pellets dosage and optimized using 32 full factorial designs. The solubility results revealed that a significant increase (p < 0.005) in the solubility of curcumin by the ratio 1:0.50 (212 ± 12 µg/ml) compared to the pure drug (90.0 ± 10 µg/ml). XRD and DSC studies confirmed the formation of amorphous curcumin, whereas FTIR elucidated weak hydrogen interactions. In-vitro dissolution study results showed the (CU:AA) ratio (1:0.50) higher percent drug release (81.61 ± 5.12%) compared to the pure drug (19.44 ± 4.60%). The developed formulations are found to be stable. Therefore, the prepared pellets of co-amorphous mixture enhance the solubility, dissolution rate, and stability of curcumin in higher pH, which will become a promising approach for combination therapy in the treatment of ulcerative colitis patients.