Levofloxacin is considered a strong weapon against several bacterial infections but its serious side effects limit its use. Curcumin, glucosamine hydrochloride (Gls) and vitamin C (Vit C) have strong effective properties. Hence, the study was carried out to assess their protective roles on levofloxacin adverse effects in immature albino rats. Fifty immature male albino rats were divided into five equal groups: I- Control group (received sterile saline solution) orally; II- Levofloxacin group (10mg/kg b.wt) intraperitoneally; III- Levofloxacin + curcumin (200mg/kg b.wt) orally; IV- Levofloxacin + Gls (500mg/kg b.wt) orally; V- Levofloxacin + Vit C (100mg/kg b.wt) intraperitoneally. Rats were euthanized on zero day and 14 days post treatment. The degree of protection was measured using calcium (Ca), phosphorus (P), alkaline phosphatase (ALP) and oxidative biomarkers levels. Furthermore, specimens from tendon, joint, ligament and cartilage were collected and subjected to routine histological technique. Levofloxacin significantly decreased Ca concentration and increased P level and ALP activity. Co-administration of curcumin, Gls and/or Vit C restored these biochemical alterations and improved antioxidant defense system. Levofloxacin produced degeneration of collagen fibers of tendons, necrosis of chondrocytes and destruction to lacunae of articular cartilage of joint, degeneration of collagen bundles of ligaments. Curcumin, Gls and/or Vit C were also markedly ameliorated histopathological effect of levofloxacin. In conclusion, curcumin, Gls and/or Vit C exerted protective actions against levofloxacin adverse effects.