Opuntia stricta is an invasive species in the Dom António Xavier Pereira Coutinho Nature Reserve (Portugal). Different chemical approaches were assessed to simultaneously manage it and preserve the natural flora of the Botanical Reserve. Glyphosate was applied at different concentrations (2.8–180 g a.e. L−1) and times of application (April, July and October) by injection into cladophyll and direct application onto areas in which the cladophyll had been cut (90 and 180 g a.e. L−1). The efficacy of the herbicide applied on the cut areas was good, but the pieces of the cladophyll that had been cut were difficult to remove and destroy. Herbicide injection of a 2 mL of solution containing 45 g a.e. L−1 glyphosate in the summer proved to be the easiest and most effective way of controlling the weed. Germination studies were carried out in order to understand the importance of seeds in the dissemination of O. stricta. The optimum constant temperature for germination was generally 20–25°C, there was a tendency towards increased germination following leaching in water for 24 h (7% germination at 20°C 12-h light) and 60-min scarification in sulphuric acid (15% at 20°C 12-h light). Although germination rates may be considered low, they do indicate that the emergence of O. stricta seedlings is possible.