PPARs are transcription factors activated by ligands, belonging to the superfamily of nuclear receptors, which are considered to be lipid sensors capable of making changes in patterns of lipid/fatty acid metabolic activity of organisms. The three isotypes (α, δ and γ) are associated with different metabolic disorders and vascular diseases as diabetes, obesity, cancer and certain mental illnesses which comprise a serious worldwide public health problem, making this class of proteins a valuable target for the pharmaceutical industry. Although it is known the importance of hPPARδ in regulating transcription of genes related to a series of metabolic processes, there is still no drug on the market directed to this receptor. Knowledge about the structure of this receptor can bring clarification able to assist the rational development of drugs. Therefore, in the present study, we sought to find structural features important for selectivity and specificity of ligand binding by the isotype δ. To this end, we determined the conditions of expression and purification of the protein hPPARδ LBD, as well as the appropriate conditions for maintaining it through the technique of circular dichroism. The oligomeric state of this receptor in solution was determined through the techniques of size exclusion chromatography and dynamic light scattering, which concluded that the protein is monomeric under the conditions tested. In addition, through a high-resolution structure of the protein hPPARδ LBD with the ligand GW 0742, we proposed the construction of two mutants, V312M and I328M, through which it was concluded that these two residues are potentially important for interaction of ligands structurally related to GW 0742 with the δ isotype. As there are few reports based on the complete structure of this receptor, and consequently about the influence of the N-terminal and DBD domains with the LBD domain, a brief study of the interaction between the nuclear receptor differential hPPARδ Full and three different cofactors in the presence of agonist and antagonist ligands were performed. For this, we determined the conditions of expression and purification of the protein hPPARδ Full, and using fluorescence anisotropy, it became clear that each cofactor has a different pattern of interaction with the protein which may be dependent on other regions of the protein in addition to those already described classically. This is a strong indication that different regions of hPPARδ can be key points in the regulatory process through cofactors.