In this study, alginate/vermiculite (Alg/VMT) hydrogel with 3-aminopropyl triethoxysilane (Alg/VSN) and tetraethoxysilane (Alg/VS) synthesized with various concentrations of CaCl2 (10 %–15 %–20 % M) to extend the release of 6-Aminopenicillanic acid (AP). Composites characterized by XRD, FTIR and BET. The result of Alg/VS composite shows an excellent loading of 243.90 mg/g through AP intercalated in the VMT layer. The equilibrium and Kinetic studies indicated that AP adsorption on Alg/VS and Alg/VSN was heterogeneous with chemical interaction. The in-vitro release Alg/VS showed a rapid burst release of 14 % in the first half an hour and only 75 % of the drug remained in the composite. Whereas, the in-vitro release Alg/VSN showed substantially less burst release with the cumulative release of 9 % (in the first 0.5 h). In-vitro release kinetics in the presence of CaCl2 concentrations showed that maximum 19 % of AP released within 12 h. The kinetic release was followed by a controlled release pattern (Korsmeyer-Peppas model) with Fick's law mechanism. The composites behaved as barriers against cell growth and had better biocompatibility against standard strains of Pseudomonas aeruginosa and Methicillin-Resistant Staphylococcus. MTT assay results from per cent cell viability composites modified by silanol groups were 96 % the means samples were nontoxic. The types of newly synthesized composites were able to finely decrease cell toxicity and improve AP release in vitro.