To enhance the affinity of the human epidermal growth receptor 2 (HER2) targeted peptide developed previously, bispecific fusion peptides <b>P1GCGT1</b> and <b>P1GCGCGT1</b> were designed using an <i>in silico</i> approach. Molecular dynamic simulation showed that both peptides strongly interacted with HER2 domains II and IV. Compared with peptides targeting each single domain, <b>P1GCGT1</b> and <b>P1GCGCGT1</b> could bind to HER2 more significantly and targeted HER2-positive cells specifically. Additionally, both peptides were used to generate peptide-drug conjugates with camptothecin (CPT), among which <b>I-1</b> and <b>I-4</b> were screened for enhanced cellular activity and selectivity. Biological evaluation demonstrated that <b>I-1</b> and <b>I-4</b> induced cell apoptosis, promoted cell cycle arrestin S-phase, and inhibited Topo I activity. The binding affinity assay and confocal analysis revealed that <b>I-1</b> and <b>I-4</b> were effective at targeting HER2. Moreover, <b>I-1</b> and <b>I-4</b> showed better stability than single targeting peptide and presented enhanced antitumor activity and safety than CPT in tumor-bearing mice.