Microalgae are a source of carotenoids, phycocyanin, phenol, amino acids, polyunsaturated fatty acids, sulfated polysaccharides, pigments, and other bioactive molecules with antimicrobial, antioxidant, antiviral, antitumor, anti-inflammatory, and fat-burning properties. The increasing incidence of infectious processes, including tuberculosis, caused by antimicrobial resistant strains of microorganisms necessitates the search for alternative sources of compounds with antimicrobial activity, including microalgae. In this study, the antimicrobial properties of marine and freshwater microalgae extracts were evaluated against Gram-positive (Staphylococcus aureus, Enterococcus faecalis, and Streptococcus pyogenes) and Gram-negative (Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa), Mycobacterium tuberculosis strain H37Rv and Mycobacterium smegmatis. Water, dimethyl sulfoxide, and ethanol were used as extractants. The obtained microalgae extract exhibited cytotoxicity against splenocytes and, to a lesser extent, against peritoneal macrophages of CBA mice. The bacteriostatic effect of the microalgae extracts against bacteria and mycobacteria was demonstrated by MTT test. In addition, activation of bacterial and mycobacterial growth was observed in a number of cases with high levels of microalgae extracts in the medium. In an expression model of tuberculosis in mice, a decrease in mycobacterial load in the lungs and spleen was observed. Thus, microalgae have moderate to weak antimicrobial activity.