Glycerol is one of the most versatile and valuable chemical substances and is utilized in a variety of commercial products with no known adverse pharmacological or environmental effects. Moreover, it exhibits good chemical stability and inertness under biological conditions. We have designed and developed Candida antarctica lipase (CAL B) catalyzed biocatalytic method to synthesize novel polymeric systems using glycerol and poly[ethylene glycol bis(carboxymethyl) ether] dimethylester. Both synthons are biocompatible, non-toxic, and are readily available. The polymerization occurs regioselectively through the primary hydroxyl groups of glycerol leaving the secondary hydroxyls for post-polymerization chemical modifications and also for attaching drugs/bioactive molecules. We have utilized these sites for the synthesis of amphiphilic polymers by attaching alkyl chains at the secondary hydroxyl groups simply by acylation. The drug encapsulation abilities of the resulting polymers have been evaluated for potential biomedical applications.