Postoperative adhesions are prone to a variety of complications, which can adversely affect the quality of life (QOL) of patients. While anti-adhesion scaffolds rapidly degrade, foreign body reactions (FBR), exaggerated inflammatory reactions, and oxidative stress may increase tissue adhesions. This necessitates the development of anti-adhesion scaffolds with multifunctional anti-inflammatory, anti-bacterial, and anti-oxidative characteristics. The objective of this study was to simultaneously leverage natural antimicrobial and anti-oxidative bioactive molecules, such as lecithin (L) and Oregano essential oil (O) to afford poly(lactic-co-glycolic acid) (PLGA)-based electrospun membranes for postoperative anti-adhesion management. A series of assays revealed a beneficial effect of L and O co-loaded membranes (P@LO) to suppress bacterial growth, reduce the proliferation of fibroblasts, and confer anti-oxidative and anti-inflammatory functionalities to membranes than that of the control (P) or only a single cue-loaded groups (P@L and P@O). The underlying molecular mechanism of the anti-inflammatory effect may be an upregulation of the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) phosphorylation. An assessment of membranes in an abdominal and a tendon adhesion model showed a significant effect of P@LO membranes to prevent post-operative tissue adhesion. The P@LO membranes were found to up-regulate the phosphorylation of Nrf2 while down-regulate the phosphorylation of nuclear factor kappa-B (NF-κB) P65. This resulted in lower expression of collagen Ⅰ (Col-Ⅰ), collagen Ⅲ (Col-Ⅲ), and alpha-smooth muscle actin (α-SMA) alongside inflammation resolution and less transition of fibroblasts to myofibroblasts. Taken together, these multifunctional scaffolds may have broad implications for postoperative adhesion management.