Objectives <p>Oral toxicities affect a high proportion of head and neck cancer (HNC) patients receiving radiotherapy, lacking reliable predictive biomarkers for incidence and severity. We investigated salivary metabolites and metabolic pathways as non-invasive predictors of radiotherapy-induced oral mucositis (OM) and candidiasis.</p> Material and methods <p>HNC patients undergoing radiotherapy were prospectively studied. Saliva samples of 45 HNC patients and 30 controls were analysed using NMR spectroscopy, and patients were assessed for oral complications during treatment.</p> Results <p>Significant metabolite differences were identified between patients with and without complications. An increased concentration of lactate (<i>p</i> &lt; 0.000), and a reduced concentration of formate (<i>p</i> = 0.018) and pyruvate (<i>p</i> = 0.045), was found in HNC patients at risk for OM during RT. Comparison of salivary metabolites between patients at risk or not risk for candidiasis presented increases in acetate (<i>p</i> = 0.005), alanine (<i>p</i> = 0.009), proline (<i>p</i> = 0.002), tyrosine (<i>p</i> &lt; 0.000), trimethylamine (<i>p</i> = 0.007) and fucose (<i>p</i> &lt; 0.000), whereas the level of citrate (<i>p</i> = 0.008) was decreased. Of the metabolic pathways, glucose-alanine cycle and thyroid hormone synthesis, were significantly different in patients at risk for candidiasis.</p> Conclusions <p>Salivary metabolomics is a promising predictive tool for radiotherapy-induced oral complications, potentially enabling early intervention and personalized supportive care.</p> Clinical relevance <p>Elevated level of salivary lactate seems to predict the development of OM, while fucosis was a sign of candidiasis. Multicentre validation studies are needed for its clinical implementation.</p>