<p>The processing and modification of microcrystalline cellulose (MCC) are highly challenging due to its highly crystalline nature restricting its broader application. This study used NaOH/urea aqueous solution for the graded regeneration of MCC, which effectively disrupted its dense crystalline structure and exposed the additional free hydroxyl groups. A modified secondary regenerated cellulose derivative (MA-SRC) with a 0.182 degree of substitution (DS) was produced using esterification with maleic anhydride. The sequential regeneration and modification with maleic anhydride increased the specific surface area of MCC from 6.87 to 8.66 m²/g. Comprehensive characterisation revealed that MA-SRC had unchanged crystalline phases, with reduced crystallinity and significantly improved hydrophobic properties. However, the difficulty in testing the mechanical properties of MCC alone (requires matrix support for moulding) required the incorporation of polylactic acid (PLA) to investigate the characteristics of the composite material further. Compared to PLA/MCC and PLA/SRC, the tensile strength of PLA/MA-SRC increased by 10.89% and 9.12%, and its elongation at break improved by 35.24% and 33.33%, respectively. Additionally, esterification significantly improved the contact angle. Consequently, these results confirmed that the synergistic graded regeneration–esterification strategy effectively enhanced the interfacial compatibility between MCC and PLA, which provided a novel approach for developing high-performance MCC-based composites.</p> Graphical abstract <p></p>