Tuesday's remarks by Abdellatif Ouahbi to Asharq TV marked the first time Rabat has publicly raised the contentious issue since Ceuta's border crisis in late July, during which an estimated 72,000 migrants briefly crossed into the enclave.
At least 96 people died in the mass border rush.
Ouahbi said his country always raised the issue of the cities' status in negotiations with Spain, with a long-term goal of achieving a resolution through dialogue.
Since its independence in 1956, Morocco has regarded Ceuta and Melilla as occupied by Spain, arguing sovereignty over them should ultimately be transferred to Rabat. Madrid considers them integral parts of its territory since the 17th and 15th centuries, respectively.
"Ceuta and Melilla aren't just Spanish; they're super-Spanish and cannot be touched," Spanish Defence Minister Margarita Robles told reporters in Ceuta when asked about Ouahbi's comments.
"Any attack on Ceuta and Melilla is an attack on Spain as a whole. It (the border crisis) must never happen again."
The Spanish government has largely praised Moroccan authorities for their co-operation in repatriating the migrants, blaming the crisis on people-smuggling mafias.
In a separate statement, Spain's Foreign Ministry said the country's territorial integrity "has not been, and will never be, discussed with anyone".
Separately, Morocco's Interior Ministry on Wednesday said it had stepped up security near the borders with Ceuta and Melilla over online calls for another mass crossing attempt on Saturday, warning it would prosecute organisers and participants.
"The ministry calls on everyone to remain vigilant and responsible and not to be drawn into such suspicious and misleading calls, given the risks they may pose to people's lives," it said in a statement, also urging Spain to accelerate the return of unaccompanied Moroccan minors in Ceuta.
Last week, Spanish Youth Minister Sira Rego said Madrid would evaluate Morocco's offer to repatriate the children on a case-by-case basis.
