Clinoptilolite, with its structural peculiarities (ion-exchange and adsorbent properties), is an excellent candidate for direct use and various modifications. In this study, we explored the effect of ion exchange and the particle size of clinoptilolite on Raphanus sativus seed germination, plant growth, physiological and biochemical characteristics of plants. Plants were grown, for three consecutive runs, on non-modified clinoptilolite, 0.9–2.5 mm (C-2.5) and 2.5–5.0 mm (C-5.0); clinoptilolite fractions modified with ion exchange with ammonium (CNH4-2.5 and CNH4-5.0); and potassium (CK-2.5 and CK-5.0) ions. Our data revealed that ion exchange with ammonium increased water-holding capacity, while potassium exchange decreased the water-holding capacity of the substrates irrespective of their particle size. The positive effect of small fractions ion-exchanged clinoptilolite (CNH4-2.5 and CK-2.5) on seed germination, during the third run, was established. The small clinoptilolite fractions favored root crop production, particularly in CK-2.5 plants only during the first run. Substantial positive effect on the content of total carbohydrates and polyphenols especially during the third run was established in plants grown on potassium-exchanged clinoptilolite. Our findings support the future exploration of clinoptilolite as a suitable substrate for plant growth in space and ground-based facilities for space-oriented experiments.