Some protozoa are responsible for human diseases, including several classified by the World Health Organization as Neglected Tropical Diseases. The search for new treatment alternatives is essential due to prolonged therapeutic regimens, adverse side effects, and diminished efficacy due to the emergence of drug-resistant strains. Microalgae and cyanobacteria represent a natural source of diverse molecules, particularly secondary metabolites, with significant potential for pharmaceutical applications. This chapter highlights the current advances in exploring the antiprotozoal potential of bioactive compounds derived from microalgae and cyanobacteria, particularly against Trypanosoma cruzi (Chagas disease), Trypanosoma brucei (sleeping sickness), Leishmania spp. (leishmaniasis), and Plasmodium spp. (malaria). Extracts of some species of microalgae and cyanobacteria were used for the screening of antiprotozoal activity as an initial indication of the presence of potentially bioactive molecules. In addition to their direct antiparasitic effects, some extracts also exhibit immunomodulatory properties that may contribute to disease control by modulating host-pathogen interactions. The majority of studies with isolated compounds tested against protozoan parasites are derived from cyanobacteria and classified as peptides, while microalgae isolated compounds remain largely unexplored in this context. Other than peptides, compounds such as pigments, polyphenols, alkaloids, and terpenes have also exhibited antiprotozoal activity. Although some compounds have shown cytotoxicity, advances in biotechnology, particularly the synthesis of structural analogs, offer opportunities to reduce toxicity and improve biological activity. Microalgae and cyanobacteria thus represent promising sources of novel bioactive molecules that may inspire the development of new drugs for the treatment of protozoan diseases.