Abstract The processing of citrus fruits leaves massive by-products. Those by-products which are considered as wastes contain a wide range of healthy bioactive compounds where carotenoids are among of them. This work aimed to study the optimum supercritical carbon dioxide (SC-CO 2 ) extraction conditions for maximization of carotenoid content and antioxidant activity for citrus by-products, using response surface methodology so that those by-products can not only be valorized effectively but also to reduce disposal problems. The effects of pressure, temperature, and mixing ratio (citrus peel-to-citrus seed mass ratio) on the recovery of carotenoids and antioxidant activity were studied. A second-order polynomial model showed a suitable fitting of the experimental values regarding the carotenoid content (R 2 = 0.9974, p 2 = 0.9919, p 2 = 0.9885, p −1 oil for carotenoid content, 0.762 mg cm −3 for DPPH, and 1.220 mg cm −3 for ABTS assay. The predicted and the experimental values were well in agreement, thus affirming the adequacy and validity of the predicted models. Overall, the combination of citrus by-products could yield the oils with good bio-activity and this could be a new valorization method.