In the current research, acyclovir-loaded microbeads were formulated via ionotropic gelation using sodium alginate-gellan gum and sodium alginate-xanthan gum. In the preparation of these acyclovir-loaded microbeads, aluminium chloride and barium chloride were used as cross-linking agents. All these ionotropically-gelled acyclovir-loaded alginate-gellan gum microbeads and alginate-xanthan gum microbeads exhibited good percent yields (85.07 ± 1.58 to 92.17 ± 3.02%) and drug entrapment efficiencies (74.09 ± 1.38 to 95.16 ± 3.37%). Acyclovir-loaded alginate-gellan gum microbeads exhibited comparatively smaller average particle sizes (0.54 ± 0.02 to 0.71 ± 0.03 mm) than those of acyclovir-loaded alginate-xanthan gum microbeads (0.60 ± 0.02 to 0.82 ± 0.04 mm). Acyclovir-loaded alginate-xanthan gum microbeads exhibited comparatively higher swelling than that of acyclovir-loaded alginate-gellan gum microbeads. A sustained pattern of acyclovir release over 240 min was noticed by these microbeads. Surface morphology analysis of the best microbeads formulation (on the basis of sustained acyclovir release data) was done by scanning electron microscopy (SEM). These kinds of ionotropically-gelled alginate-based microbeads might be advantageous to facilitate enhanced patient compliances with minimal dosing frequency and enhanced oral bioavailability.