Downstream costs represent one of the main obstacles to enabling microalgae to become widespread. The development of an economical, easily scaled-up strategy could reduce the overall process costs. Here, different flocculants were tested on different microalgae strains and a cyanobacterium. The results indicate that flocculation could be an alternative to centrifugation, as CaCl2 induced a complete flocculation of green and red marine strains (96 ± 4% and 87.0 ± 0.5%, respectively), whereas Chitosan was the only agent able to induce flocculation on the cyanobacterium (46 ± 1%). As for the thermoacidophilic red microalga, 100% flocculation was achieved only by increasing the pH. Carotenoids were extracted from the flocculated biomass, and the strategy improved with the use of the wet biomass. The results indicate that flocculation does not affect carotenoid yield, which is at least the same than that obtained upon centrifugation and extraction from the wet biomass. Then, for the first time, the biological activity of the extracts obtained from the flocculated biomasses was evaluated. The results indicate that only the green microalga extract shows increased antioxidant activity. In conclusion, this work highlights that a general downstream procedure cannot be developed for microalgae strains but should be rationally tailored.