The emergence of multidrug-resistant ESKAPE infections has emerged as a serious public health threat. Nosocomial infections are most often caused by ESKAPE bacteria. To combat multidrug-resistant ESKAPE, the research team used Valeriana Wallichii extracts and nanoparticles. The well diffusion technique was used to test antimicrobial activity on Muller Hinton agar medium. The FTIR, SEM and XRD techniques were used to characterize the nanoparticles synthesized in an environmentally benign manner. Both NPs performed better than extracts made with methanol and water in this investigation. The smallest zones of inhibition were shown against A. baumannii and Enterobacter cloacae, whereas the largest zones of inhibition were seen against E. faecium. However, NPs synthesized from shoot extracts exhibited remarkable effects against all MDR ESKAPE infections, with zones of inhibition of 23, 20, 12, 18, 22 and 14mm, respectively. Although E. faecium. had the largest inhibitory zone in both methanolic root and shoot extracts (19mm and 22mm, respectively), K. pneumonia and E. cloacae had the smallest zones when tested with these solvents. Water-based extracts inactivated multidrug-resistant bacteria. Our research show that extracts and nanoparticles have stronger antibacterial efficiency because biologically active substances including Terpenoids, Alkaloids, Phenol and Pholobutannins affect people and microbe.