Platelet-rich plasma (PRP) composites of various cytokines and growth factors which have the potential to activate and speed the process of wound repair. Sildenafil also is a potent stimulator of angiogenesis which favors its potential effects on wound healing in several models. Existing work planned to examine the effectiveness of topical application of PRP and/or sildenafil citrate hydrogel (SCH) in a non-splinted excision skin wound model. Adult male rats were allocated into control, PRP, SCH, and PRP/SCH groups. On the 7th and 14th days, blood and tissue samples were collected for hematobiochemical, histopathological, and immunohistochemistry analyses. PRP and/or SCH topical treatments caused an enhancement of wound healing parameters, including a rapid switch from inflammatory phase to connective tissue stage evident by less systemic hematological changes and decreased values of proinflammatory cytokines (IL-6, TNF-α, and IL-1β) and C-reactive protein (CRP) on the 7th or 14th days post-wounding. Also, tissue hydroxyproline, collagen, nitrite, and total protein contents were higher in therapeutically handled wounded rats. Histologically, PRP- and/or SCH-treated wounded rats exhibited less necrosis, inflammation, and fibrin with a higher level of granulation tissue formation on the 7th day post-wounding and abundant collagen remodeling, epithelization, and vascularization on the 14th day relative to control. Interestingly, combined PRP and SCH treatment was more efficient in wound healing scoring with less inflammation, more collagen remodeling, and more epithelization. Our findings confirm the effectiveness of PRP and/or SCH as a topical wound healing treatment, with better skin wound healing with their combination.