This study provides a comprehensive review of scientific evidence addressing preventive measures for white spot lesions (WSLs) that develop as a consequence of fixed orthodontic treatment. WSLs, which arise from enamel demineralization, create both aesthetic and functional complications. The review focuses on assessing the efficacy of various preventive approaches aimed at minimizing WSL occurrence during orthodontic therapy. A detailed literature search was performed using MeSH terms including “white spot,” “fixed orthodontic treatment,” “CPP-ACP,” “topical fluoride,” and “demineralized lesion,” combined with the Boolean operator ‘AND’. Databases such as PubMed, EMBASE, Scopus, and OpenGrey were searched for studies published between January 2014 and September 2024. Inclusion criteria encompassed studies evaluating preventive strategies for reducing WSL risk in patients treated with fixed orthodontic appliances. Out of 41 retrieved studies, 17 met the selection criteria based on methodological quality and relevance. Multiple preventive modalities were identified as effective in mitigating WSL formation. Topical fluoride, especially in high-concentration varnish form, showed significant efficacy, with several studies reporting superior results compared to alternative treatments. Casein phosphopeptide–amorphous calcium phosphate (CPP-ACP) and its fluoride-enriched variant (CPP-ACPF) promoted enamel remineralization, particularly when used alongside fluoride toothpaste. Additionally, high-fluoride toothpaste and acidulated phosphate fluoride mouthwash reduced lesion incidence, reinforcing the role of consistent oral hygiene compliance. Periodic professional applications of fluoride varnish further improved preventive outcomes. The prevention of WSLs is essential for maintaining both the aesthetic and clinical success of orthodontic therapy. Combining fluoride-based treatments with CPP-derived compounds provides substantial protective benefits. Nonetheless, patient awareness and adherence to prescribed oral hygiene measures are fundamental. Continued research should aim to assess the long-term comparative efficacy of existing interventions and develop innovative approaches for WSL prevention.
