Speaking on Saturday at Mumoni in Kitui County during the burial of Pastor William Muthengi, Kalonzo said the two officials should be held to the same standard as the administration they serve.
"Hawa watu kama Duale wasiwasumbue, yeye na katibu mkuu wa UDA wanafaa wajiuzulu, they are not fit to hold public office, they are as incompetent as their top boss," he said.
The former Vice President said State House should remain a symbol of national unity and service to all Kenyans, warning that it must not be reduced to a hub of cartels or division.
"State House is not a place of glory, it is a place of work, it is not a place for cartels," Kalonzo said.
He also issued a pointed warning over the continued cases of abductions, saying such actions must come to an end and cautioning the President against turning security agencies on government critics.
"President Ruto alisimama jana kusema hakuna more goons, kumbe goons walikuwa wa Ruto. The next time utashika watu wetu na kuwaweka kwa Subaru is the day utajua Kenyans wamekosa imani na wewe," he said.
Turning to the recent Ol Kalou by-election, Kalonzo said the contest had set the tone for future polls and demonstrated the will of the people, framing it as a signal of a shifting political mood among young voters.
"Uchaguzi ujao hautakuwa uchaguzi wa kawaida, utakuwa kama wa Ol Kalou. Serikali ilitumia hadi supplementary budget, lakini vijana wakasema hawatavumilia tena. Ufisadi umekuwa mwingi, hakuna kazi, hatutaki mharibu nchi halafu mwende zenu," he said.
He added: "Wameonyesha Kenya mpya, kuna mfumo mpya wa siasa nchini."
Kalonzo's remarks add to a growing chorus of condemnation against Duale over a viral video in which the Cabinet Secretary is alleged to have compared the Somali and Kikuyu communities, recounting what he described as historical discrimination against Somalis under former Presidents Jomo Kenyatta, Mwai Kibaki and Uhuru Kenyatta while crediting President William Ruto with ending those practices.
Speaking in vernacular in Mandera County, Duale reportedly told his audience that leaders from the Mount Kenya region had done little for the North compared to the current administration. The National Cohesion and Integration Commission has since opened a probe into the remarks, which it is investigating as potentially ethnically inciteful.
Duale has defended himself, insisting he was misquoted and that his comments were taken out of context. The video also drew sharp criticism in the Senate, where lawmakers from both sides of the House warned that such rhetoric risked reopening the wounds of the 2007/08 post-election violence ahead of the 2027 General Election.