Background <p>Radiotherapy (RT) is associated with significant acute and long-term side effects that may impair oral health-related quality of life (OHRQoL). This systematic review aimed to synthesise the existing evidence on how RT affects OHRQoL in patients with head and neck cancer (HNC).</p> Methods <p>This review was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and registered in PROSPERO (CRD42023448568). A systematic search was carried out in PubMed, Scopus, Web of Science, and EBSCO host using combinations of terms related to RT, HNC, and OHRQoL. Only observational studies involving adult patients treated with RT were included. Data extraction and quality assessment were performed independently by two reviewers.</p> Results <p>A total of 5100 records were identified, with 73 studies meeting the inclusion criteria. The results were categorised into impacts during RT, and short-term (&lt; 6&#xa0;months), and long-term (≥ 6&#xa0;months), impacts after RT. During RT, OHRQoL was most affected by oral mucositis (OM), pain, xerostomia/dry mouth, and taste dysfunction (TD). Short-term after RT the most notable effect on OHRQoL was pain, xerostomia/dry mouth and sticky saliva, similar to outcomes during RT. In the long term, xerostomia/dry mouth and TD remained the predominant issues, often persisting for years after treatment and contributing to sustained reductions in OHRQoL.</p> Conclusion <p>RT for HNC is associated with poorer OHRQoL. However, these findings should be interpreted with caution, as all included studies were observational and of moderate quality. Xerostomia/dry mouth and related oral complications were the most consistently reported contributors to reduced quality of life (QoL). These findings underscore the need for individualised, interprofessional care strategies that integrate clinical assessments with patient-reported outcomes (PROMs).</p>