Nanotechnology is known as the science of recent era and its applications have been extended in various fields like chemistry, biology and physics. This field of science deals with nanoparticles (NPs) having dimension between 1-100 nm. Different types of NPs are currently being synthesised. Among them, silver nanoparticles (AgNPs) have known to possess the antimicrobial potential due to their large surface area and small size. Pakistan is an agricultural country accounted for 18.9% of the GDP. Citrus is an important horticultural and economically important small sized tree fruit crop around the world. Average yield of Citrus reticulata (Mandarin) in Pakistan is low as compared to the developed country. The low yield of Mandarin is due to attack of different microbial diseases. Among different microbial diseases, canker is major disease of Mandarin and 30% is lost due to canker disease. The major objective of this study is to find the potential role of AgNPs for improving the tolerance against canker disease. AgNPs were synthesised using leaves extract of Moringa oleifera as the main reducing and stabilising agent. The synthesised AgNPs were characterised through UV-Visible spectroscopy, Zeta Analyser, SEM, XRD and EDX. Different concentrations (10, 20, 30, and 40 ppm) of the synthesised AgNPs were exogenously applied on Mandarin to record disease incidence against canker disease. It was found that no concentration of synthesised AgNPs completely inhibited canker disease. The effect of AgNPs on the intensity of canker disease varied greatly and 30 ppm was found to be the most suitable concentration for enhancing the tolerance against canker disease. Different enzymatic (CAT, SOD, and POD) and non-enzymatic (TPC, TFC, Proline content, MDA, protein content) activities were also explored in response to various concentrations of AgNPs under canker stress. It was found that plants which were treated with pathogen only showed the enhanced enzymatic and non-enzymatic activities. Fruit quality (Juice content, pH, Vit C) and fruit productivity (yield per plant, fruit weight, ED, PD and PT) parameters were significantly enhanced when plants were exogenously sprayed with 30 ppm AgNPs. Proteome analysis was also done in the leaves and seeds samples of mandarin and functional categorization were done through MapMan Bin Codes Software. It was found that plant defense related proteins were more up-regulated and stress related proteins were down-regulated in response to 30 ppm AgNPs under biotic stress. So, it can be concluded that plant based synthesised AgNPs have the potential to enhance the tolerance against canker disease. Further studies are required to explore the molecular mechanism and interaction of NPs inside the cell.