<p>The nopal (<i>Opuntia ficus-indica</i> (L.) Mill., Cactaceae) is an endemic plant from the American continent whose agroindustry generates a high amount of by-products. To reduce waste and improve the sustainability of this agroindustry, some by-products and fruits at different stages of maturation were analyzed in terms of their chemical content, dermatological properties, and photoprotective effects. Factors like total phenolic content, antioxidant activity by different assays, and inhibition of collagenase, elastase, hyaluronidase, and tyrosinase were tested in both aqueous and organic extracts of cladodes, flower buds, and prickly pear (epicarp and mesocarp) at different stages of maturation. Then, the ROS production and photoprotective effect of HaCaT death induced by UVA radiation were measured for extracts with the highest antioxidant and enzyme inhibitory activity related to aging. Thirty-one and twenty-one compounds were identified in aqueous and organic extracts, respectively, by GC–MS. The most prominent compounds in aqueous extracts were sugars, organic acids, and polyphenols. In organic extracts, these compounds were the diterpenes, organic acids, polyphenols, and phytosterols. The antioxidant capacity was generally more significant in the aqueous extracts of unripe epicarp, cladodes, and flower buds. These extracts presented the highest total phenolic content values between 14,111 ± 76 and 16,754 ± 117&#xa0;mg GAE/100&#xa0;g. The aqueous extract of ripe mesocarp exhibited a strong inhibitory effect on tyrosinase (100% at 250&#xa0;μg/ml), which can be tentatively attributed to a synergistic effect among the detected inhibitors. Furthermore, flower buds and unripe epicarp extracts showed a protective effect on HaCaT cells from UVA-induced oxidative damage. In this way, the applicability of by-products and fruits at different stages of ripening from <i>O. ficus-indica</i> in the production of natural cosmetic ingredients is suggested.</p> Graphical Abstract <p></p>