Polylactic acid (PLA), due to its high mechanical strength, biocompatibility, excellent biodegradability and good processing characteristics, can be used to print the bone scaffold with complex structures, but the poor cell affinity and inflammation resulted by the acidity of intermediate produce still pose a challenge. To address these issues, o-carboxymethyl chitosan (CMC) was used to modify PLA, and the phase miscibility of PLA/CMC blends with different component ratios was investigated by a multi-scale method. Here, molecular simulation and experimental methods were applied to predict the miscibility of polylactic acid and o-carboxymethyl chitosan blends. Results indicated that PLA and CMC are miscible when the concentration of CMC in blends below 20 wt %, and partially miscible at 30 wt% concentration of CMC, but completely immiscible at higher CMC content (> 30 wt%). Conclusions from this work can be used to forecast the miscibility of PLA/CMC composites at different compositions and can provide a scientific basis for formula designs of PLA/CMC polymer composites for 3D printing artificial bone scaffolds.