She explained the limitations associated with separating long DNA chains via gel electrophoresis dynamics,[5][6] which was of great importance to the Human Genome Project.

Olvera de la Cruz discovered that counterions induce the precipitation of strongly charged polyelectrolytes by including electrostatic correlations in the analysis.

She and her students and postdocs discovered that electrostatics leads to spontaneous symmetry breaking in ionic membranes such as viral capsids[14] (for which they were awarded the 2007 Cozzarelli Prize[15]) and in fibers.

[16][17] They also demonstrated the spontaneous emergence of various regular and irregular polyhedral geometries in closed membranes with non-homogeneous elastic properties such as bacterial microcompartments, including carboxysomes,[18] via a mechanism that explains observed shapes in crystalline shells formed by more than one component such as archaea and organelle wall envelopes as well as in ionic vesicles.

Olvera de la Cruz and Qiao found that the binding of the SARS-CoV-2 spike protein receptor-binding domain (RBD) to the human cell receptor hACE2 can be strongly decreased by mutating or blocking the polybasic cleavage site (known as the furin cleavage site),[25] providing a mechanism to decrease COVID 19 infection, as subsequently demonstrated experimentally.