Ca2+ signaling via voltage-gated Ca2+ channels has been suggested to play prominent roles in the development and degeneration of neurons. To elucidate the specific role of L-type CaV1.3 channels, we designed and tested a series of peptides, derived from the competitive mechanism between calmodulin (CaM) and distal carboxyl tail (DCT) of L-type CaV channels, with the capability to enhance or inhibit calcium dependent inactivation (CDI), a negative-feedback mechanism regulating actual Ca2+ flux through the channel. Under whole-cell patch-clamp, CDI of rat/human CaV1.3 was strongly attenuated for co-transfections of CaV1.3 with derivative peptides from DCT of CaV1.4. Such inhibitory peptides, termed as iCaMp (inhibitors of CaM pre-association), exerted significant inhibitions on the number and averaged length of dendrites if expressed in cultured cortical neurons, supposedly as the downstream consequence of CaV1.3 / Ca2+ dysregulations. Moreover, peptide ICDIV41A, with single point mutation on iCaMp, completely lost its effects on dendritic growth of cortical neurons, in consistence with its loss of CDI effects on recombinant CaV1.3 channels. On the other hand, peptide modulators of eCaMp (enhancers of CaM pre-association) opposite to iCaMp have also been sought after. The prototype of eCaMp significantly enhanced CDI of CaV1.3 from the intermediate level up to the extreme level, at which apparent DCT effects diminish. Taken together, our peptides provide an innovative way to perturb Ca2+ signaling specific to L-type CaV1.3 channels, shedding light on physiological roles of neuronal CaV1.3 channels as well as its potential relevance with neural degenerative diseases such as Alzheimer’s.