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• Synthesis of low molar mass Hydroxypropylmethyl Cellulose. • Low molar mass HPMC was produced by partial enzymatic depolymerization. • Phase separation was performed to separate different molar mass of HPMC. • Low molar mass HPMC with M w below 20,000 g mol−1 and dispersity less than 1.5 was produced. 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 (M w) 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 M w 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. [ABSTRACT FROM AUTHOR]