The current study examined the combined effects of feeding rates and feeding types on the water quality, growth performance, digestive enzymes, blood parameters, and liver antioxidant enzymes of Nile tilapia (Oreochromis niloticus) fingerlings reared under a biofloc system. A 3 × 2 factorial experimental design was used with three feeding rates (2%, 3%, and 4%) and two feeding types (sinking or floating feed), comprising six treatments with three replicates. Fingerlings with an initial body weight of 4.50 ± 0.25 g were stocked in eighteen circular plastic tanks (0.5 m3) at a stocking density of 35 fish per tank fed three times a day at 10:00, 12:00 and 15:00. Starch was added to all treatments as an organic carbon source at a C/N ratio of 10:1. The phytoplankton community was determined to consist of twenty-two species, including individuals from the classes Cyanobacteria, Chlorophyceae, and Bacillariophyta. The most common phytoplankton classes were Chlorophyceae, followed by Cyanobacteria, and fish-fed floating feed at a feeding rate of 2% of total biomass yielded the greatest number of phytoplankton communities. Eight zooplankton species belonging to rotifers and protozoa were identified during this experiment. The highest values of final body weight, weight gain, and specific growth rate were recorded for a fish-fed floating diet with the highest feeding rate (4% of biomass). The highest hepatosomatic index (HIS) was detected in a fish-fed floating diet at a rate of 4% of total biomass. Though fish-fed sinking feed with a 4% biomass feeding rate presented the highest spleen index (SI). The highest significant (P < 0.05) level of amylase was found in fish-fed sinking feed at a 4% feeding rate. While lipase activity was higher (P < 0.05) in the group fed floating feed at a feeding rate of 3% of total biomass. Feeding rates, feed types, and their interactions had no appreciable effect (P > 0.05) on hemoglobin (Hb), hematocrit (Hct), and red blood cells (RBCs). Feeding rate, feed type, and their interactions had no significant impact (P > 0.05) on serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), or albumin, but feeding rates or feed types had an effect (P < 0.05) on total protein and globulin (P < 0.05). The highest levels of growth hormone (GH) (P < 0.05) were found in fish-fed either sinking feed at a feeding rate of 2% or floated feed at a feeding rate of 3% of total biomass. The fish group fed floating or sinking feed at a feeding rate of 2%, floating feed at 3%, and sinking feed at 4% recorded the highest high-density lipoprotein (HDL-C) values with an insignificant difference. Considering the liver's antioxidant enzymes, the highest catalase (CAT) and glutathione (GSH) levels were shown in fish that received either sinking or floating feed at feeding rates of 2% and 3%, respectively. Whereas, the lowest melanodialdehyde (MDA) was found in fish-fed sinking feed at a feeding rate of 3% of total biomass. According to the study's findings, the biofloc system significantly improved both the water quality and the efficiency of Nile tilapia. In addition, feeding tilapia 4% floating feed resulted in maximum feed consumption with minimal waste, improved nutritional efficiency and feed conversion efficiency, lowered production costs, and lessened water pollution.