Poly(lactic-co-glycolic acid) (PLGA) has been widely used in biomedical and pharmaceutical applications because of its satisfactory biocompatibility and biodegradation profile. However, its applications for tissue engineering scaffolds have been plagued by inflammatory responses that can lead to fibrotic encapsulation. p-Hydroxybenzyl alcohol (HBA) is a phenolic compound in herbal agents that exerts antioxidant and anti-inflammatory activities. In this work, we developed PLGA blend films containing HBA-incorporated peroxalate polymer (HPOX) and investigated the effects of HPOX on the local inflammatory responses to PLGA in vitro and in vivo. The PLGA/HPOX blend films had no adverse effects on cell viability and elicited a significantly lower production of pro-inflammatory mediators such as tumor necrosis factor-${alpha}$ and reactive oxygen species than PLGA films. We also found that PLGA/HPOX blend films implanted into a rat had significantly diminished inflammatory responses. PLGA/HPOX blends appear to be a promising approach for tissue engineering applications due to their excellent biocompatibility and anti-inflammatory effects.