Chirality plays an essential role in chemical and biological sciences. At the molecular level, the effects associated with this phenomenon can be studied by using the well-established technique of molecular dynamics simulations. In this work, we present several approaches suited for the molecular dynamics-based free energy calculation in chiral systems. In particular, we have proposed and tested the following strategies relying on the application of general, enhanced sampling methods: (i) biased sampling in the two-dimensional space, along the coordinates defined by the values of the selected torsional angles; (ii) biased sampling in the one- or two-dimensional space, along the path-based coordinate(s); (iii) rational alteration of the system's Hamiltonian in order to enable the interconversion between stereoisomers and reweighting the biased distribution of configurations; (iv) using the free energy landscape generated within approaches (i) or (ii) as time-independent bias in order to further improve sampling efficiency and simultaneously account for multiple chiral centers. All approaches have been tested on a set of model compounds (fenoterol, fructofuranose, and bromochlorofluoromethane), demonstrating the good performance but also some differences in the range of their applicabilities.