Feed additives are critical components for poultry health and the economic viability of antibiotic-free poultry production. The aim of the present study is to evaluate the safety of a novel algal-derived feed additive, a dried biomass powder produced from Chlamydomonas reinhardtii strain crAL082, modified to express an N-acetylmuramoyl-L-alanine amidase (EC 220.127.116.11) and a lysozyme-type enzyme (EC 18.104.22.168). A 42-day oral toxicity study showed that the crAL082 dried biomass powder was fully tolerated by broiler chicken based on the lack of detrimental effects found in performance, mortality, hematology, blood clinical chemistry, and histopathologic results compared with those of a nontreated control group, resulting in a “No Observed Adverse Effect Level” of 5000 ppm, the highest dose tested. The study demonstrates the first-ever safety result of a C. reinhardtii microalgae dried biomass powder used as a feed additive in broiler chickens. Furthermore, safety is shown for the two additional enzymes expressed within the C. reinhardtii crAL082 strain and ingested by the birds.