Reactive comb (RC) polymers were synthesized by copolymerizing methyl methacrylate (MMA) with glycidyl methacrylate (GMA) and a kind of MMA macromer. The obtained molecules had both epoxide groups and long PMMA side chains distributed randomly along the PMMA backbone. The synthesized RC polymers were applied as compatibilizers in an immiscible poly(l-lactic acid)/poly(vinylidene fluoride) (PLLA/PVDF) system. Compared to their linear counterparts, only 1 wt % of RC polymers with appropriate length of side chains significantly reduced the size and enhanced the uniformity of the PVDF dispersed phase in PLLA matrix and the RC-compatibilized blends exhibited a significant improvement in fracture strain. The higher compatibilization efficiency of RC polymers was ascribed to the existence of PMMA side chains, which improved the stability of RC polymers at the interface of immiscible blend, and this was demonstrated by transmission electron microscopy.