A detailed theoretical investigation of specific rotation is carried out in solution for nine flexible molecules of biological importance. Systematic search for the main conformers is followed by time-dependent density functional theory (TD-DFT) calculations of specific rotation employing a wide range of basis sets. Due to conformational flexibility of the compounds under study, the possibility of basis set size reduction without deterioration of the results is investigated. The increasing size (d-)aug-cc-pVXZ (X = D, T, Q) bases of Dunning et al., and the ORP basis set, recently developed to efficiently provide molecular specific rotation, are used for this purpose. The polarizable continuum model is employed at all steps of the investigation. Comparison of the present results with the available data obtained in a vacuum reveals considerable differences, the values in solution being much closer to the experimental specific rotation data available. The ORP basis set proves to be competitive with the d-aug-cc-pVDZ set of Dunning in specific rotation calculations carried out in solution. While having the same number of functions, the former yields, in general, results considerably closer to the reference triple-ζ values. We can thus recommend the ORP basis set to study the optical rotation in conformationally flexible molecules in solution.