Comorbidity between borderline personality disorder (BPD) and alcohol use disorder (AUD) is high and relevant as alcohol consumption seems to worsen BPD symptomatology. One of the newest treatments for AUD, nalmefene, may be useful to improve BPD symptoms not only indirectly by reducing alcohol consumption but also directly by acting on the opioid system as this system has been related to specific BPD symptoms. This open-label study aimed at evaluating the efficacy of an 8-week nalmefene treatment in reducing alcohol consumption in individuals with BPD and comorbid AUD. A secondary objective was to assess its efficacy in improving general BPD symptomatology and specific behaviors (self injury and binge eating). Eighteen out of the 25 patients with BPD and comorbid AUD enrolled in the study completed all the assessment points. After 8 weeks, a significant reduction was observed in alcohol consumption, BPD global symptomatology, self-injurious behavior, and binge eating. No serious adverse effects were reported; however, five participants experienced mild side effects, resulting in withdrawal from the study in two cases. According to our results, nalmefene may be a safe and effective drug for treating patients with BPD and comorbid AUD. Controlled clinical trials are needed to support our findings.