Optical coherence tomography (OCT) has become a popular modality in the dermatology discipline due to its moderate resolution and penetration depth. OCT images, however, contain a grainy pattern called speckle. To date, a variety of filtering techniques have been introduced to reduce speckle in OCT images. However, further improvement is required to reduce edge smoothing and the deterioration of small structures in OCT images after despeckling. In this manuscript, we present a novel cluster-based speckle reduction framework (CSRF) that consists of a clustering method, followed by a despeckling method. Since edges are borders of two adjacent clusters, the proposed framework leaves the edges intact. Moreover, the multiplicative speckle noise could be modeled as additive noise in each cluster. To evaluate the performance of CSRF and demonstrate its generic nature, a clustering method, namely k-means (KM), and, two pixelwise despeckling algorithms, including Lee filter (LF) and adaptive Wiener filter (AWF), are used. The results indicate that CSRF significantly improves the performance of despeckling algorithms. These improvements are evaluated on healthy human skin images in vivo using two numerical assessment measures including signal-to-noise ratio (SNR), and structural similarity index (SSIM).