The main problem associated with mangosteen (Garcinia mangostana L.) in the postharvest period is fruit rot caused by Lasiodioplodia theobromae, which results in pericarp hardening, poor quality, and short storage life. Silver nanoparticles (AgNPs) constitute a potential agent for curbing microbial infections, especially fungal infections. In the in vitro test conducted in this study, 270 ppm AgNPs completely inhibited mycelium growth and spore germination (100 %) in L. theobromae, similar to the results obtained using 200 ppm fungicidal carbendazim. For the in vivo test, the concentration of AgNPs was increased to 300 ppm to provide a strong inhibitory effect against fungal infection on mangosteen fruit. The results showed that treatment with AgNPs significantly decreased the disease index (DI) in the artificially inoculated mangosteen fruit stored at 25ºC, and AgNP residue in the fruit was found to be 3.3 mg kg-1, which conforms to the Environmental Protection Agency (2009) regulations. Furthermore, the effects of AgNPs on fruit rot disease and plant defense-related enzymes were investigated with regard to naturally infected mangosteen stored at 13ºC for 30 days, as compared to fungicide-treated fruits and non-treated fruits (control). The results revealed that AgNP treatment resulted in an eight-fold reduction in fruit rot disease, whereas fungicidal treatment resulted in only a 2.46-fold disease reduction compared to the result in the control group. Also, AgNP treatment induced plant defense-related enzyme activities: phenylalanine ammonia-lyase (PAL), peroxidase (POD), chitinase (CHI) and β-1,3-glucanase (GLU), and ɑ-mangostin content (a major phenolic compound in pericarp). Further, the effect of AgNPs on the physiology and quality of fruits was measured and compared with the non-treated fruits. The results showed that AgNP treatment lowered ethylene production and rate of respiration, which resulted in a reduction in weight loss and pericarp hardening. AgNP treatment was also found to maintain pericarp color, chlorophyll content in calyx as well as total soluble solids (TSS), titratable acidity (TA), and anthocyanin content in the pericarp. This result implies that AgNPs constitute an effective and safe treatment modality for controlling fruit rot disease, reducing pericarp hardening, and maintaining the quality of mangosteen fruit.