Over the years, several biopolymers have widely been exploited for the delivery of small-molecule drugs, particularly owing to their outstanding biocompatible and biodegradable characteristics. In this context an array of drug molecules has been chemically conjugated with various biopolymers and the resulting conjugates could slowly elute their cargos following cleavage of the biopolymer-drug linkages under physiological conditions. These conjugates offer numerous advantages over their therapeutic precursors. For instance, the conjugates could enhance water solubility and bioavailability of the drugs, improve their pharmacokinetic and biodistribution profiles, protect them from deactivation, and facilitate their transport to the targeted sites, which eventually augment the bio-performances of the drugs. The present chapter reviews recently reported covalent conjugates based on biopolymers and small-molecule drugs and their therapeutic benefits.