The incidence of anterior cruciate ligament (ACL) injuries is on the rise due to increased physical and sports activities. Thus, ACL reconstruction is a common surgical procedure to treat ACL ruptures, however, it has a failure rate of 0.7–21% and only 63% of the patients are able to recover to their pre-injury sport level. Orthobiologics, including platelet-rich plasma (PRP), growth factors, and stem cells, are being explored as alternative treatment methods to maximize the results and reduce surgical morbidity and healing time. PRP is derived from a blood sample with high platelet concentration and containing growth factors and interleukins. Studies have shown that PRP can improve the maturation of ACL reconstruction but more research is required to support its use in ACL surgery. On one hand, growth factors play a crucial role in ligament healing and PRP, which contains high levels of growth factors, has been shown to stimulate angiogenesis and encourage cell proliferation. On the other hand, stem cells have the ability to differentiate into other cell types and limit the inflammatory microenvironment during acute ligament injury. Ligament-derived stem cells show better potential for lineage-specific tendon/ligament differentiation when used with differentiation inducers. The use of stem cells in ACL reconstruction is still in the early stages of investigation. Therefore, cell therapy agents have shown promising results in preclinical models, but more research is required to determine the most effective biological agents for treatment.