In a nationwide broadcast, the first since his return, President Buhari reiterated that the nation's unity is non-negotiable.
Nnamdi Kanu's Indigenous People of Biafra (IPOB) and various youth groups in Nigeria's north have been very vocal since the president's departure on May 7, 2017.
Kanu wants a Biafra nation carved out of Nigeria's present structure.
In a nationwide broadcast Monday morning, Buhari said: "My dear citizens, I am very grateful to God and to all Nigerians for their prayers. I am pleased to be back on home soil among my brothers and sisters".
Buhari returned to Nigeria on Saturday, August 19, after spending 103 days in the UK where he was tending to his faltering health.
The president's ailment remains undisclosed; even in this morning's address.
"In the course of my stay in the United Kingdom, I have been kept in daily touch with events at home. Nigerians are robust and lively in discussing their affairs, but I was distressed to notice that some of the comments, especially on social media, have crossed our national red lines by daring to question our collective existence as a nation. This is a step too far.
"In 2003 after I joined partisan politics, the late Chief Emeka Ojukwu came and stayed as my guest in my hometown Daura.
"Over two days we discussed in great depth till late into the night and analyzed the problems of Nigeria. We both came to the conclusion that the country must remain one and united.
"Nigeria's unity is settled and not negotiable. We shall not allow irresponsible elements to start trouble, and when things get bad they run away and saddle others with the responsibility of bringing back order, if necessary with their blood".
The president also said every Nigerian has a right to do business anywhere.
"Every Nigerian has the right to live and pursue his business anywhere in Nigeria without let or hindrance.
"I believe the very vast majority of Nigerians share this view. This is not to deny that there are legitimate concerns. Every group has a grievance. But the beauty and attraction of a federation is that it allows different groups to air their grievances and work out a mode of co-existence.
"The National Assembly and the National Council of State are the legitimate and appropriate bodies for national discourse. The national consensus is that, it is better to live together than to live apart.
"Furthermore, I am charging the Security Agencies not to let the successes achieved in the last 18 months be a sign to relax".
The president added that his administration will reinvigorate its war against Boko Haram and rein in other security challenges.
"Terrorists and criminals must be fought and destroyed relentlessly so that the majority of us can live in peace and safety.
"Elements of Boko Haram which are attempting a new series of attacks on soft targets; kidnappings; farmers versus herdsmen clashes in addition to ethnic violence fuelled by political mischief makers. We shall tackle them all".
Buhari concluded by saying he's so glad to be back home.
"Finally, dear Nigerians, our collective interest now is to eschew petty differences and come together to face common challenges of economic security, political evolution and integration, as well as lasting peace among all Nigerians.
"I remain resolutely committed to ensuring that these goals are achieved and maintained. I am so glad to be home.
"Thank you and may God bless our dear Nation", President Buhari said.