Reported herein is the first combination of resonant acoustic mixing (RAM) and controlled ring-opening polymerization (ROP) to deliver fully sustainable, end-functionalized, biodegradable polymers via a manufacturing route with a much-reduced environmental impact. This includes the successful use of agriculturally sourced functionalized initiators (terpene alcohols) in ROP synthesis of cyclic esters to generate an array of novel, biodegradable polyesters applicable to numerous biomedical applications, such as drug delivery. Furthermore, RAM was utilized as a novel mixing technique, resulting in a synthetic process that was conducted: (a) with minimal use of toxic, flammable, costly, and environmentally detrimental solvents, (b) in the absence of organometallic catalysts, and (c) with significantly shorter ROP reaction times and temperatures. Consequent comparison with conventional magnetic stirring or sonication-based mixing methods showed that RAM allowed the more facile, kilogram-scale synthesis of polyesters via reactions conducted at room temperature rather than 150 °C and without the need for a metal catalyst. As a proof of concept, the polymers were used to encapsulate bovine serum albumin as a model protein, and its release was measured using an automated, high-throughput protein assay. This study demonstrated that the headgroup chemistry appears to affect the release rate of protein from the polymers.