The aquaculture industry has explored alternative protein and lipid sources for aquaculture feed to reduce costs and promote sustainability. Microalgae is a desirable feed ingredient because it is grown in high volume and can be selected for high levels of lipids and protein. Additionally, microalgae have been recently explored as a prebiotic to promote the health of fish species through the modulation of the intestinal microbiota. This study investigated the use of microalgae as fishmeal and fish oil replacements and its effect on the intestinal histology and microbiota of hybrid tilapia (Oreochromis niloticus x O. mossambicus). Feed intake and body weight were recorded weekly and intestinal samples were collected monthly and processed for microbiota analysis using metagenomics and histological analysis of the intestinal epithelia. Tilapia growth performance was significantly higher in the 100% algae-based diet compared to the fishmeal and fish oil control (P>0.05), suggesting that microalgae can completely replace fishmeal and fish oil in the tilapia diets without negative impact. Microalgae inclusion into the tilapia diets did not significantly alter the overall intestinal microbiota. However, several species were significantly different between treatments, most notably an increase in Parabacteroides goldsteinii in the 100% algal inclusion. P. goldsteinii is a known beneficial microbe in the human GI tract, thus the inclusion of algae in the diets may be used as a strategy to modulate the gut health of Tilapia. Additionally, several novel species were reported in tilapia including the two most common species across all treatments, Mycobacterium pinnipedii , a closely related species to the tuberculosis-causing M. tuberculosis , and the non-tuberculosis causing, M. brasiliensis. Histological results did not show a significant difference between treatments, suggesting that algae inclusion in the diet does not negatively affect the health of tilapia.