Objectives This study aimed to assess self- and proxy-rated changes in the oral health-related quality of life (OHRQoL) in adult patients with intellectual disabilities after dental treatment in general anesthesia. Methods The OHRQoL in 52 adult patients with intellectual and developmental disabilities was assessed prior to dental treatment in general anesthesia (t0), 2 to 3 (t1) and 12 weeks (t2) postoperatively. Therefore, patients and primary cargivers were surveyed using either the 5-item short form of the Oral Health Impact Profile translated into easy language (OHIP-G5-easy, self-rating, n = 27) or the 14-item short form of the Oral Health Impact Profile (OHIP-G14, proxy-rating, n = 51), respectively. OHIP-G5-easy and OHIP-G14 summary scores were statistically analyzed with non-parametric mixed effects models and spearman correlation (p < 0.05). Additionally, the effect of demographic, anamnestic, oral health and treatment factors on QHRQoL or on changes of OHRQoL were analyzed using univariate and multivariate ordinal logistic regressions (p < 0.05). Results Self- (t0: 5.8 +/- 4.6, t1: 4.3 +/- 5.9, t2: 2.0 +/- 3.9) and proxy-ratings (t0: 18.8 +/- 11.6, t1: 10.1 +/- 11.2, t2: 2.7 +/- 5.3) revealed a significant improvement of OHRQoL after dental treatment in general anesthesia. Data showed a moderate correlation (p < 0.001, r(Sp) = 0.43). OHRQoL at baseline was affected by the etiology of cognitive impairment and by the periodontal status (OHIP-G14). Improvement of OHRQoL was associated with the etiology of cognitive impairment (OHIP-G14) and the extent of dental treatment (OHIP-G5-easy). Conclusion Self- and proxy-ratings revealed a significant improvement of OHRQoL in patients with intellectual disabilities after dental treatment in general anesthesia.