Protein and peptide-based therapeutic agents have unique physiochemical properties such as high molecular weight, short half life, requirement of a sustained plasma level for the desired therapeutic effect, liable to physical and chemical instability by gastric enzymes and harsh acidic environment as well as first pass metabolism, which makes their delivery a challenge. The delivery of proteins and peptides using various routes of administration like oral, nasal, rectal, pulmonary, buccal, vaginal and transdermal route is found to exhibit limitations, poor permeability and degradation being major limitations. Use of parenteral route is found to overcome these problems but patient compliance is poor due to the need for frequent administration. Use of control delivery for these drugs using smart polymers seems promising as they overcome the limitations posed by other routes of delivery. Smart polymers increase patient compliance, maintain stability of the drug, and maintain drug level in therapeutic window and are easy to manufacture. Different types of smart polymerbased delivery systems, such as sensitive to temperature, phase, pH, electric charge, light, and biochemicals, and their application in controlling the release of the incorporated drug to obtain a sustained plasma level has been discussed. Smart polymers, however, face challenges with regard to high burst release, unpredictable behavior in later part of biphasic release profile, overall drug release kinetics, conformational stability during processing, and preserving biological activity after getting released. Several patents overcoming these inherent problems associated with smart polymers have been reviewed. At the end, the future direction and potential of smart polymer-based delivery system for drug delivery has been presented in brief.