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Purpose This study was conducted to evaluate the clinical peri‐implant soft tissue changes during the first year after occlusal loading and the ridge base relation after 3 years for mandibular computer‐aided design and computer‐aided manufacturing (CAD‐CAM) screw‐retained implant‐supported hybrid prosthesis of polyetheretherketone (PEEK) framework utilized with All‐on‐Four treatment concept. Materials and methods Sixteen completely edentulous patients were rehabilitated by four implants following the All‐on‐Four protocol. After 3 months, the definitive prosthesis was constructed to be a screw‐retained CAD‐CAM milled framework from the modified PEEK (BioHPP), bonded to polymethylmethacrylate teeth and a pink shaded indirect light‐polymerized nanofilled composite resin imitating the soft tissues. Peri‐implant soft tissue changes regarding plaque, bleeding, gingival scores, and probing depth were evaluated at prosthesis insertion (T0), 6 months (T1), and 12 months (T2) after insertion. Also, monitoring of the ridge base relation was performed using cone beam computed tomography at time of insertion (T0), and 1 year (T1), 2 years (T2), and 3 years (T3) after mandibular fixed detachable All‐on‐Four framework insertion. Using Shapiro‐Wilk tests using SPSS® software version 22 (SPSS Inc., Chicago, IL), all clinical data were nonparametric, while the ridge base relation data were parametric. Results There were statistically significant differences regarding a plaque, gingival, and bleeding scores for all implants with the advancement of time. However, there was a statistically insignificant difference regarding probing depth in the posterior implants (p = 0.581). Regarding ridge base relation, there was a significant difference between observation times only in the anterior ridge area in between the two anterior implants (p = 0.011). Conclusions Within the limitations of the study, the full‐arch PEEK framework of fixed‐detachable, hybrid prosthesis used with the All‐on‐Four concept for rehabilitation of mandibular edentulous arches is an acceptable treatment approach. Based on the stable ridge base relation posteriorly found in this study, less stress is distributed to the underlining bone due to the shock‐absorbing ability of PEEK. Special considerations for frequent soft tissue follow‐up and regular maintenance of oral hygiene measures are recommended.