Mushroom production and consumption are gaining increased interest due to their unique flavor and nutritional value. However, in the mushroom industry, large amounts of by-products are generated, which have a high negative environmental and economic impact. In this study, an osmotic dehydration process followed by hot-air-drying was applied to mushroom stems to produce dried mushrooms as the end product. The osmotic dehydration conditions (concentration of hypertonic solution, specifically, 10–30% maltodextrin and 20–40% oligofructose; a treatment time of 40–80 min; and a temperature range of 30–50 °C) were optimized using response surface methodology (RSM). The results showed that a four-factor three-level Box–Behnken experimental design was effectively implemented to evaluate the effect of the process parameters and identify the optimal osmotic dehydration conditions for producing osmotically dehydrated mushrooms. The main factor affecting mass transfer was the osmosis temperature, and the optimal conditions were found to be 38 °C, 40% oligofructose and 19.3% maltodextrin as the osmotic agents, and 80 min of immersion time. Moreover, the results showed that osmotic pretreatment, in the optimal conditions, significantly reduced the required drying time of the by-products compared to traditional hot-air-drying, especially at milder drying temperatures. Consequently, the required energy was also reduced by at least 40% at 50 °C.