In the current study some derivatives of naphthalenylmethylen hydrazine were synthesized and possible in vitro hCA I and II enzymes inhibition effects were investigated. The designed compounds were synthesized by condensation of phenylhydrazine with 1-naphthaldehyde or 6-methoxy-2-naphthaldehyde and eight compounds (1a-h) were obtained. The novel Schiff bases derivatives (compounds 1a-1h) were effective inhibitors of the cytosolic carbonic anhydrase I and II isoforms (hCA I and II) with Ki values in the range of 80.60 ± 17.90 to 492.53 ± 95.23 nM for hCA I, 102.88 ± 18.44 to 461.09 ± 102.50 nM for hCA II. 1f compound shows a remarkable inhibitory effect of hCA I and hCA II isoenzymes among the new synthesized compounds. The new derivatives of naphthalenylmethylen hydrazine can be a potent inhibitor of both cytosolic CA isoenzymes which are commonly used in the pharmaceutical industries and medical areas.