They include businessman Juma Mukhwana of the Jubilee Party and veteran journalists David Makali and Boniface Nyongesa.
Mr Nyongesa recently resigned as the head of Sulwe FM, a Bukusu vernacular radio station owned by Royal Media Services.
Mr Makali will be vying for the seat for the second time on the Amani National Congress ticket after he was defeated in the 2013 by-election Mr Wetang’ula.
This was after former Webuye MP Musikari Kombo successfully challenged in court Mr Wetang'ula's victory in the March 4, 2013 elections.
“Mr Wetang’ula should prepare himself for a resounding defeat,” said Mr Mukhwana.
“He should not be cheating us that he is going for the presidency but returns to vie for a smaller seat, he should be disappointed, I will give him a run for his money.”
Resident Benard Wakamala said Mr Wetang’ula is a big let-down to the Luhya community and should not be taken seriously at all.
“He launched his presidential ambition at Muliro Gardens in Kakamega, now he is telling us that he wants to defend his senatorial seat. He is a joke,” he said.
“Let us vote for other serious people who can drive the development agenda of this country.”
Fred Wekesa, a Ford-Kenya supporter, said the politician had made the right decision to defend his seat.
“I see nothing wrong,” he said.