Osteoporosis is characterized by low bone mass and bone tissue microarchitectural deterioration with increased fracture risk in numerous populations. Probiotics are reported to be a potential biotherapeutic for the prevention and treatment of osteoporosis. In this study, the IL-10 secretion properties of probiotics were simulated in vitro and the potential applications of the novel strain Lactiplantibacillus plantarum 622 were investigated in an in vivo osteoporosis model. Female Sprague-Dawley rats were ovariectomized (OVX) and orally administered Lp. plantarum GMNL-662 or alendronate for 14 weeks. The Lp. plantarum treatment group exhibited an increase in the level of fecal Lp. plantarum, Lactobacillus, and Lachnospiraceae. Bone marker analysis indicated improvements in the levels of osteocalcin and N-terminal telopeptides in the Lp. plantarum treatment group. Compared with the OVX control group, the Lp. plantarum treatment group exhibited marked improvements in femur bone mineral density, trabecular bone volume, trabecular number, and lumbar vertebrae. Moreover, biomechanical three-point bending testing indicated considerably higher improvements in femur maximum load, stiffness, and energy to maximum load in the Lp. plantarum treatment group than in the OVX control group. Quantitative polymerase chain reaction analysis indicated reduced expression levels of OVX-induced IL-1, IL-6, TNFα, and RANKL and increased expression levels of IL-10, TGF-β, and osteoprotegerin in the Lp. Plantarum treatment group. In summary, Lp. plantarum GMNL-662 exhibits high probiotic potential and potentially influences osteoimmunity through the modulation of proinflammatory cytokines and bone metabolism-related markers.