Prodrug is an effective way to improve the oral absorption of the drugs which belong to BiopharmaceuticalsClassification System (BCS) class III and IV. This reviewaddresses the progress of the oral prodrugs in recent years, mainly including classical prodrug design and targeted prodrug design. Classical prodrug design is focused on modification of oil-water partition coefficient or decrease the metabolism of parentdrugs. Targeted prodrug design is actively concerned with the physiological characteristics of the gastrointestinal tract to target tissues, enzymes and influx transporters. Intestinal influx transporter, the peptide transporter-targeted prodrug design is a growing field of the research of oral prodrugs recently. Challenges of prodrug strategy, design and investigation in vivo are also discussed.