Matricaria chamomilla is extensively consumed as a tea or tonic. Despite its widespread use as a home remedy, relatively few trials evaluated its benefits in nephro protection. Hence, this study evaluates the protective role of M. chamomilla in cisplatin nephrotoxicity rat model. The study was conducted on 32 rats divided into four groups. The first group (G1) was injected with saline intra-peritoneally (IP); G2 was injected with 5 mg/kg cisplatin on day 0 of the experiment and repeated four times, with five days free interval. G3 and G4 were injected daily with M. chamomilla (50 mg/kg) IP, starting five days before the experiment (-5 day); in addition, G4 was injected with cisplatin. On day 16, animals were scarified and serum and/or kidney tissue was used to determine: (a) kidney function tests (serum urea, creatinine, gamma glutamyl transferase (GGT), NAG, β-gal), (b) oxidative stress indices (NO, LPO), (c) antioxidant activities (SOD, GSH, total thiols), (d) apoptotic indices (Cathepsin D, DNA fragmentation) and (e) mineral (calcium). M. chamomilla significantly increased the body weight, normalized the kidney functions, improved the apoptotic markers, reduced the oxidative stress markers and corrected the hypo-calcemia that resulted from cisplatin nephrotoxicity. M. chamomilla is a promising nephro-protective compound reducing cisplatin nephrotoxicity most probably by its antioxidant activities and inhibition of gamma glutamyl transferase activity.