Aim The aim of this study was to evaluate the clinical performance of lycopene‐enriched virgin olive oil in spray form used to treat patients with drug‐induced xerostomia, comparing this with a placebo spray. Materials and Methods This double‐blind, randomized clinical trial included elderly subjects with drug‐induced xerostomia ( n = 60). Resting salivary flow was measured using the draining technique. The Xerostomia Inventory (XI) was used to assess symptoms and the Oral Health Impact Profile 14 (OHIP‐14) to assess patient quality of life. Evaluations were made before and after 12 weeks of product/placebo application. Results Sixty patients took part in the study. Symptoms improved among the treatment group ( n = 30) after 12 weeks in the following XI domains: ‘Rate the difficulty you experience in speaking because of dryness’ ( P = 0.03); ‘Rate how much saliva is in your mouth’ ( P = 0.03); and ‘Rate the dryness of your lips’ ( P = 0.04). The placebo group ( n = 30) underwent improvements in: ‘Rate how much saliva is in your mouth’ ( P = 0.02) and ‘Rate the dryness of your mouth’ ( P = 0.01). A significant improvement ( P = 0.001) in oral‐related quality of life (OHIP‐14) was identified in the treatment group, while no significant differences were observed in the placebo group ( P > 0.05). Conclusion The topical application of lycopene‐enriched virgin olive oil and its placebo counterpart improved xerostomia‐related symptoms significantly (but not salivary flow rate) in patients with drug‐induced xerostomia.