BACKGROUND: Pharmacological means of anchorage control can improve patient compliance. Bisphosphonates could be helpful in orthodontic anchorage control if their actions could be localized to limit (or control) unwanted tooth movement while not interfering with the desired tooth movement. OBJECTIVE: This systematic review aimed to examine and evaluate the quality of all animal studies that reported the effect of locally administered bisphosphonate on limiting orthodontic tooth movement. DATA SOURCES: An electronic search was conducted in the PubMed-Medline, Scopus, Google Scholar, and Cochrane databases till May 2022, using the keywords anchorage, anchorage loss, molar movement, posterior tooth movement, incisor movement, incisor retraction, anterior retraction, unwanted tooth movement, tooth displacement, tooth movement forward, bisphosphonate, local bisphosphonate administration, bisphosphonate injection, and bbisphosphonate vestibular induction. Only studies involving localized bisphosphonate administration for anchorage purposes were taken into account. DATA SELECTION: Animal studies that simulated orthodontic tooth movement after localized injection of bisphosphonate and evaluated the rate of tooth movement were included in the review. DATA EXTRACTION AND ANALYSIS: The quality of the studies was assessed by using ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments). Bias in the studies was analyzed by SYRCLE's tool (Systematic Review Centre for Laboratory Animal Experimentation) for risk of bias. RESULTS: The search strategy yielded 925 titles. After screening, 908 articles were discarded because they did not fulfill the inclusion/exclusion criteria based on the title and abstract. The remaining 16 articles were read entirely, of which nine were excluded as they involved systemic administration of bisphosphonates. Finally, after careful consideration, seven papers that met our inclusion criteria were included in the qualitative analysis. The majority of studies were assessed to have an uncertain risk of bias, with just one deemed low risk of bias. CONCLUSION: This systematic review found that bisphosphonates limit orthodontic tooth movement around the application site without affecting adjacent sites. More potent bisphosphonates in smaller doses or less potent bisphosphonates in higher frequencies have been proposed to improve outcomes. However, the data quality is insufficient to recommend a protocol for bisphosphonate administration for anchoring control. Long-term studies evaluating various types, frequencies, and dosages of bisphosphonates are required to clarify the effects on orthodontic tooth movement. REGISTRATION NUMBER FOR PROSPERO: CRD42021224033