The projection of molecular processes onto a small set of relevant descriptors, the so-called reaction coordinates or collective variables (CVs), is a technique nowadays routinely employed by the biomolecular simulation community. In this work, we implemented two CVs to manipulate the orientation (i.e., angle) (μ⃗a) and magnitude (|μ⃗|) of the electric dipole moment. In doing so, we studied the thermodynamics of water orientation under the application of external voltages and the folding of two polypeptides at zero-field conditions. The projection of the free-energy [potential of mean force (PMF)] along water orientation defined an upper limit of around 0.3 V for irrelevant thermodynamic effects. On the other hand, sufficiently strong μ⃗a restraints applied on 12-alanine (Ala12) triggered structural effects because of the alignment of local dipoles; for lower restraints, a full-body rotation is achieved. The manipulation of |μ⃗| produced strong perturbations on the secondary structure of Ala12, promoting an enhanced sampling to its configurational space. Rigorous free-energy calculations in the form of 2-D PMFs for deca-alanine showed the utility of |μ⃗| as a reaction coordinate to study folding in small α helices. As a whole, we propose that the manipulation of both components of the dipole moment, μ⃗a and |μ⃗|, provides thermodynamics insights into the structural conformation and stability of biomolecules. These new CVs are implemented in the Colvars module, available for NAMD and LAMMPS.