Aim: The aim of the present study was to measure dental anxiety levels and oral health-related qualities of life (OHRQoL) in patients with periodontitis compared to healthy controls and to analyze their association with various demographic, clinical and periodontal parameters. Methods: Fifty-five patients with periodontitis and 56 healthy controls were enrolled. Collected data included demographics, smoking habits, numerical rating scale (NRS), Corah’s Dental Anxiety Scale (DAS) and Oral Health Impact Profile-14 (OHIP-14), DMFT index (Decayed, Missing and Filled Teeth), Plaque Index (PI), probing depth (PD), bleeding on probing (BOP), and radiographic bone loss. Results: Periodontitis patients exhibited statistically significant higher scores in the total DAS and in almost of single DAS domains. Compared to the control group, periodontitis patients exhibited worse OHIP-14 global as well as in all individual OHIP-14 domains scores. Among both periodontitis and control patients, the physical pain domain was where the highest impact was recorded, while the lowest impact was recorded in the functional limitation domain. Conclusion: Periodontitis patients were positively associated with higher levels of dental anxiety and worse OHRQoL. Self-perception of dental anxiety and OHRQoL should be regarded as an integral element in routine diagnostic work-up process of periodontal diseases. This study showed that for a nationally representative sample of the southern Italian population population, periodontal disease was significantly associated with the domains of OHRQoL.