Regenerated cellulose and alginate have been increasingly utilized to prepare medical textiles due to their biocompatibility. A 33-face-centered design was proposed to prepare and optimize alginate and lornoxicam (LRX)-loaded textiles using bamboo and modal regenerated cellulose fibers. The effects of different factors (bamboo%, X1, LRX amount, X2, and sonication time, X3) on the textiles' performance were studied. The textiles were evaluated for physical, mechanical, and surface properties, LRX loading%, particle size, zeta-potential, dissolution, and release kinetics. Bamboo% exhibited a significant negative effect on the textile weight (p-value = 0.0376). LRX amount showed significant positive effects on flexural rigidity, tensile strength, and particle size (p-value = 0.0379, 0.0086, and 0.0004, respectively). The sonication time showed a significant negative effect on LRX particle size and a positive effect on the magnitude of zeta-potential (p-value = 0.0204, and 0.0208, respectively). All the samples showed high stability as indicated by the absolute values of Zeta-potential (>51.8 mV) which might be attributed to the effect of alginate as a stabilizer. The studied formulations followed different LRX release models suggesting erosion, Fickian, non-Fickian diffusion, and super case II mechanisms. A multiple-response optimization was employed, and the proposed design of experiments enabled the prediction of the optimal factors' levels required for the target responses.