Hybrid hydrogels containing alginate (Alg) and poly­(N-isopropylacrylamide) (PNIPAAm) chains as natural and synthetic components, respectively, were crosslinked using double and triple pairs of the crosslinkers Ce3+/Ce4+, laponite (LP) RD, and N,N’-methylenebisacrylamide (BIS). (Alg/PNIPAAm)-Ce3+ and (Alg/PNIPAAm-PNIPAAm)-Ce3+ double- and triple-network structures were prepared using multivalent cerium ions (Ce3+), multifunctional laponite layers (L), and/or neutral tetrafunctonal BIS molecules (B). Compressive Young’s moduli, E, were tuned by the type/concentration of crosslinkers and crosslinking procedures and the concentration of Alg chains. The antibacterial activity of positively charged ions and molecules is due to the electrostatic attraction with the negatively charged bacterial cell walls. In the current study, we report the antibacterial activity on Escherichia coli of Ce3+ ions in the absence and presence of gentamicin sulfate (GS) for double and triple networks. Nonbacterial areas, which are called inhibition zones, around the disks, and compressive E moduli of the single and double PNIPAAm and Alg/PNIPAAm networks crosslinked by LP RD and containing Ce3+/Ce4+ions in free and ionically bonded states, respectively, were higher than those of the ones crosslinked with BIS. Moreover, BIS- and LP RD-crosslinked single PNIPAAm hydrogels displayed larger inhibition zones than those of Alg/PNIPAAm hybrids, supporting the antibacterial activity of free Ce3+/Ce4+ ions diffused together with GS molecules. On the other hand, antibacterial activities of GS + Ce3+-loaded triple networks were much lower than those of their double counterparts because the increase in the structural complexity reduced the co-emission of antibacterial agents.