Inflammatory diseases, such as cardiovascular disease (CVD), are significant concerns to the medical community and the health of societies worldwide. Strategies to reduce the inflammation associated with these diseases are of increased importance given the serious nature of CVD treatments, which are often risky and invasive. Some naturally occurring substances represent an untapped resource for potentially therapeutic compounds that may possess anti-inflammatory characteristics, such as resveratrol, a polyphenol-derived compound found in a variety of fruits. A goal of the study is to mimic an inflammatory response by inducing cell stress using Tumor Necrosis Factor-α (TNF-α) in vascular endothelial cells in vitro. The endothelial cells were treated with resveratrol to assess the anti-inflammatory properties of the compound. Resveratrol was shown to reduce cell stress without causing morphological abnormalities. In addition, wound healing, a critical step in the immune response to injury involving inflammation, was modeled using a scratch wound assay. Wound healing was enhanced in vascular endothelial cells. Lastly, we use polymeric biomaterials and a Chandler Loop to model resveratrol’s use in biomaterial rejection, another process highly dependent on inflammation levels. Resveratrol was shown to attenuate biomaterial rejection through significant inhibition (p < 0.01) of inflammatory cell attachment to polymeric biomaterials, including in the physiologically relevant model of a Chandler Loop. Taken together, our results suggest that resveratrol possesses potent anti-inflammatory characteristics in vascular endothelial cells and macrophages. These results take the field a step further in the prospect of using resveratrol for its anti-inflammatory properties and to increase the lifespan of implantable medical devices.