The oral administration is the route preferred by patients due to its multiple advantages. In the case of biopharmaceuticals, due to their low stability and absorption in the intestine, these molecules must be administered by injectable routes. To circumvent these problems, several strategies have been studied, among which the use of nanosystems, such as polymersomes, can be highlighted. In this work the potential of poloxamer 401 polymersomes as a system for oral delivery of antibodies was evaluated. IgG-FITC-loaded poloxamer 401 polymerosomes were initially used to assess whether it improves intestinal epithelial permeation in Caco-2 cell monolayers. Subsequently, epithelial/macrophage co-culture model was used to evaluate the ability of poloxamer 401 polymersomes containing adalimumab to reduce proinflammatory cytokine levels. The data showed that polymersome-encapsulated IgG increased the transport across intestinal Caco-2 monolayers 2.7-fold compared to the antibody in solution. Also, when comparing the groups of blank polymersomes with polymersomes containing adalimumab, decreases of 1.5-, 5.5-, and 2.4-fold in TNF-α concentrations were observed for the polymersomes containing 1.5, 3.75, and 15 µg/mL of adalimumab, respectively. This could indicate a possibility for the oral administration of biopharmaceuticals which would revolutionize many conditions that require the systemic administration such as in inflammatory bowel disease.