Low molar mass (LMM) biopolymers are highly required to design functional nanomaterials, which mainly find application in biomedical fields. However, the synthesis of LMM polymer is a challenging task. In this work, we report a partial enzymatic depolymerization process which allows to produce a series of LMM hydroxypropylmethyl cellulose (HPMC) polymer, with a weight average molar mass (Mw) under and over 10,000 g mol−1 and low dispersity (Ɖ < 1.5). Variation of the starting HPMC grade, reaction time, and enzyme concentration were the key parameters to control the Mw and yield of the target molecules. This approach provides a versatile way of producing LMM HPMCs with varying degrees of substitution, and having a single reactive aldehyde function at one chain extremity. LMM HPMC can find for instance application as building blocks for the development of new functional molecular architectures.