Amoxicillin trihydrate-loaded hydrogel beads were prepared and characterized as a controlled drug delivery system to improve patient compliance. An ionotropic gelation process was used to prepare the hydrogel beads using calcium chloride (CaCl2) as a crosslinking agent. The effects of CaCl2, sodium alginate, poloxamer 407 (PL) concentration, and preparation temperature were investigated. Spherical hydrogel beads were obtained with high encapsulation efficiency (85.74±1.09) %. FTIR analyses confirmed the compatibility of amoxicillin with the used excipients. In vitro swelling and cumulative drug release studies were performed over 24 hours in HCl medium, pH 1.2. Prepara-tion temperature was found to influence both the index of beads swelling (SI) and the cumulative release of amoxicil-lin. The study demonstrated the capability of PL to enhance the cumulative release of amoxicillin, correlating with swelling behavior. The proposed hydrogel beads have the potential as a promising drug delivery system for controlled release of amoxicillin, over 24 hours, and thus reduced dosing frequency.