The present invention discloses an “Improved Oral Targetted Drug Delivery System (O-TDDS)” particularly suited for delivery of drugs having activity against the diseases located in the colon e.g. colon cancer, ulcerative colitis, protozoal infections etc. The system comprises two elements or parts viz. microspheres (drug+natural polymers such as guar gum or xanthan gum) and probiotics. Both the elements are packed together in a single, pharmaceutically acceptable oral dosage form such as a capsule. The system offers distinct advantages of drug delivery without undesirable side-effects of diarrhea, nausea or vomiting commonly encountered in case of anti-cancer drugs such as 5-Fluorouracil.