This study aimed to prepare and characterise polylactic acid (PLA) reinforced with cellulose nanofibre (CNF) from a Pennisetum purpureum-based composite scaffold and determine its structural and mechanical properties. Porous scaffolds with CNF compositions of 5‒20 wt% in the PLA matrix were developed using solvent casting and particulate leaching of its porogen at 90 wt% of loadings. Morphology studies using field emission scanning electron microscopy revealed that the scaffolds had well-interconnected pores with an average pore size range of 67‒137 μm and porosity >76%. X-ray diffraction confirmed the interconnectivity and homogeneity of the pores and the fibrous structure of the scaffolds. The compressive strength of the fabricated scaffolds varied between 2.34 and 6.66 MPa, while their compressive modulus was between 1.95 and 6.04 MPa for various CNF contents. Furthermore, water absorption and thermal degradation studies showed that the scaffold had good hydrophilicity and improved thermal stability. These findings highlight the need to modify the pore structure and mechanical performance simultaneously for tissue engineering. Thus, this study concludes that the developed PLA scaffolds reinforced with CNF from Pennisetum purpureum are potential candidates for cell attachment and extracellular matrix generation.