Skin expansion is a well-established technique in plastic surgery, and recent studies have highlighted its potential in promoting hair regeneration. This study aimed to explore how the mechanical and optical properties of skin change during a prolonged stretching process. A hybrid method was developed to assess, in vivo, the effects of an 8-day skin stretching protocol—previously used in hair regeneration research—on the dorsal skin of mice. This method combined mechanical and optical measurement systems. Tensile stress–strain curves were generated using a spring-based setup, while optical properties such as scattering and birefringence were analyzed with a polarimetry imaging system that incorporated the Mueller matrix (MM) and Mueller matrix polar decomposition (MMPD) methods. The results showed that Young's modulus increased from approximately 5 kPa on day 1 to 60–100 kPa by days 6–8, indicating collagen fiber straightening and increased stiffness. Optical analysis revealed greater anisotropy in both scattering and birefringence, as reflected by changes in MM elements and MMPD results. These changes suggest skin adaptation and regeneration, particularly within the first 24 h of stretching. Interestingly, alterations in optical properties closely mirrored changes in mechanical properties, pointing to a coordinated process of structural remodeling and functional adaptation in the skin. These findings offer valuable insights into skin remodeling and adaptation, which could guide future tissue engineering strategies.