Clinical indications for the newly released Ti-Zr (Roxolid®) alloy mini-implants (MDIs) aimed for overdenture (OD) retention in subjects with narrow alveolar ridges are not fully defined. The aim of this study was to analyze peri-implant and posterior edentulous area microstrains utilizing models of the mandible mimicking a “real” mouth situation with two (splinted with a bar or as single units) or four unsplinted Ti-Zr MDIs. The models were virtually designed from a cone beam computed tomography (CBCT) scan of a convenient patient and printed. The artificial mucosa was two millimeters thick. After MDI insertion, the strain gauges were bonded on the oral and vestibular peri-implant sites, and on distal edentulous areas under a denture. After attaching the ODs to MDIs, the ODs were loaded using a metal plate positioned on the first artificial molars (posterior loadings) bilaterally and unilaterally with 50, 100, and 150 N forces, respectively. During anterior loadings, the plate was positioned on the denture’s incisors and loaded with 50 and 100 N forces. Each loading was repeated 15 times. The means with standard deviations, and the significance of the differences (two- and three-factor MANOVA) were calculated. Variations in the MDI number, location, and splinting status elicited different microstrains. Higher loading forces elicited higher microstrains. Unilateral loadings elicited higher microstrains than bilateral and anterior loadings, especially on the loading side. Peri-implant microstrains were lower in the four-MDI single-unit model than in both two-MDI models (unsplinted and splinted). Posterior implants showed higher peri-implant microstrains than anterior in the four-MDI model. The splinting of the two-MDI did not have a significant effect on peri-implant microstrains but elicited lower microstrains in the posterior edentulous area. The strains did not exceed the bone reparatory mechanisms, although precaution and additional study should be addressed when two Ti-Zr MDIs support mandibular ODs.