Skin wounding is a serious public health issue, especially when considering factors that accelerate tissue recovery. Consequently, the use of photodynamic therapy (PDT) as an effective wound-healing treatment has attracted more scientific attention. Although assessing the wound healing rate is crucial for appropriate monitoring of the probability of wound healing and evaluating the treatment efficiency, the currently used techniques lack the ability to provide such information. Therefore, this study has two aims, first, it contributes to the development of a new image-guided biospeckle system for quantitative monitoring of skin wound healing rate. Second, it evaluates the potential of using a novel synthesized PDT-mediated polyethylene glycol fabric with methylene blue (PEG-MB) hydrogel nanocomposite in accelerating wound healing. The proposed imaging system initially acquires raw biospeckle images from the wound regions of adult healthy albino mice treated with the synthesized hydrogel nanocomposite. Each raw biospeckle image is then converted into maps of morphological local-gradient matrices implemented from the combination of dilation and erosion operations at different radii up to 25 pixels. Subsequently, their intensity histogram statistics are computed, taking central moments as the feature set. Final characterization is achieved via a linear combination of the biospeckle statistics maintaining as much variance as possible using principal component analysis (PCA). The results confirmed by cytokine concentration measurement and histological investigation demonstrate that the innovative biospeckle image-guided system is ideal for investigating wound healing and suggest the potential of the hydrogel nanocomposite as an active dressing.