The skin injuries pose a substantial public health challenge, not only due to their physical trauma but also the accompanying pain and complexities in wound healing. In the current research, Inula helenium extract and lidocaine were loaded into electrospun PVA/calcium alginate nanofibers to promote skin wounds healing and alleviate the resulting pain. Various in vitro experiments were utilized to characterize these dressings. Wound healing potential of these constructs and their analgesic effects were studied in a rat model of skin wounds. Our developed scaffolds released the loaded drugs in a slow manner and showed antioxidative and anti-inflammatory activities. Fiber size measurement showed that drug-loaded and drug-free scaffolds had around 418.025 ± 140.11 nm and 505.51 ± 93.29 nm mean fiber size, respectively. Bacterial penetration assay confirmed that drug-loaded scaffolds reduced bacterial infiltration through the matrices. Wound healing study showed that on day 14th, the dressings loaded with inula helenium extract and lidocaine could close the wounds up to 91.26 ± 5.93%. In addition, these scaffolds significantly reduced the animals pain sensitivity. ELISA assay results implied that these dressings modulated inflammation and reduced tissue’s oxidative stress.