This chapter emphasizes on improving the pharmacological activity, i.e. potency, of peptide drugs. It concentrates the discussion on enhancing the pharmacokinetic properties of peptide drugs with an emphasis on membrane permeability. “Lipinski’s Rule of Five” described the physicochemical features for a drug’s pharmacokinetics in the human body, including its absorption, distribution, metabolism and excretion (ADME). The chapter discusses the solubilizing agents that are applicable to all routes of administration, namely parenteral, topical and enteral. Most peptide and protein drugs are restricted to the parenteral route because they are susceptible to enzymatic degradation during absorption or cannot be efficiently absorbed into the systemic circulation, due to their large molecular sizes 15 and charge issue. Most type 1 diabetes mellitus patients have to subcutaneously inject insulin multiple times each day while changing their sites of administration, i.e. site rotation, to keep the skin healthy.