To assess the clinical efficacy of a novel, organic olive oil-based denture adhesive and its effect on growth in maxillary edentulous individuals wearing complete dentures, individuals were selected from two dental schools in Portugal and Spain. Twenty-eight complete dentures were relined, following a standardized protocol. The novel product (test) was compared with a commercialized adhesive (control) and Vaseline (placebo) randomly assigned in a cross-study design. The retention resistance was measured with a gnathometer and a dynamometer. The patients related outcome evaluations with a five-point questionnaire, and the growth in a Sabouraud dextrose agar (SDA) medium was used to evaluate differences between the placebo and experimental product. Twenty-three participants were included. The dynamometer evaluation showed significant differences between not using a denture adhesive and using either (experimental, = 0.03; control, = 0.04) and no significant differences between the two adhesives ( > 0.05). In the subjective analysis, the experimental adhesive showed a significantly longer effectiveness ( = 0.001), and the control reported better results in taste ( = 0.03) and in chewing ( = 0.001). The test adhesive showed better ( < 0.001) growth inhibition. The experimental adhesive showed longer effectiveness than the control and the placebo with a better inhibition capacity for the growth of . Patients reported better abilities for speech, chewing, taste, and retirement in the control adhesive.