Glycyrrhiza glabra Linn (liquorice) has been widely used for therapeutic purposes to treat digestive disorders, immunomodulatory disorders, inflammatory disorders, diabetes, viral infections, and cancer. Liquorice contains a wide variety of bioactive compounds, including glycyrrhizin, flavonoids, and terpenoids. Several factors compromise their therapeutic efficacy, such as poor pharmacokinetic profiles and physicochemical properties. Therefore, to improve its overall effectiveness, liquorice solid dispersion (LSD) was incorporated into biopolymer-based guar gum-grafted-2-acrylamido-2-methylpropane sulfonic acid (Guar gum-g-AMPS) hydrogels designed for controlled delivery via the oral route and characterized. The qualitative analysis of LSD revealed 51 compounds. Hydrogel structural properties were assessed for their effect on swelling and release. The highest swelling ratio (6413 %) and drug release (84.12 %) occurred at pH 1.2 compared to pH 7.4 (swelling ratio of 2721 % and drug release of 79.36 %) in 48 h. The hydrogels exhibited high porosity (84.23 %) and biodegradation (9.30 % in 7 days). In vitro hemolysis tests have demonstrated the compatibility of the hydrogel with blood. CCK-8 assay confirmed the biocompatibility of the synthesized hydrogel using osteoblasts and RIN-m5f cells. LSD exhibited good anti-inflammatory activity when loaded into hydrogels after being subjected to protein denaturation experiments. Moreover, LSD-loaded hydrogels have good antioxidant and antibacterial properties.