Two Japanese cabinet ministers have resigned over the dubious use of political funds, dealing Prime Minister Shinzo Abe his biggest setback since he took office in December 2012.

The resignations of the two women, including the high profile trade and industry minister, could complicate tough decisions on key policies, including whether to go ahead with an unpopular plan to raise the sales tax and planned restarts of nuclear reactors shut down after the 2011 Fukushima disaster.

Abe hopes to contain the damage through swift replacements of the two, but the opposition is looking for other potentially vulnerable ministers also appointed in an early September cabinet reshuffle. Further resignations could raise doubts about Abe's own future, some political experts said.

"There are more than two (other) ministers with regard to whom there are suspicions," Yukio Edano, the opposition Democratic Party's second-in-command, told reporters. "We will coordinate our actions among opposition parties, point out the problems and ask for explanations about the other ministers."

He did not identify the ministers nor explain how the opposition planned to seek any explanations.

Trade and industry Minister Yuko Obuchi, 40, the daughter of a prime minister and tipped as a future contender to become Japan's first female premier, tendered her resignation after allegations that her support groups misused political funds.

Just hours later, Justice Minister Midori Matsushima also resigned.

The opposition Democratic Party had filed a criminal complaint against Matsushima, accusing her of violating the election law by distributing paper fans to voters.

Obuchi and Matsushima were two of five women appointed by Abe in the cabinet reshuffle, a move intended to boost his popularity and show his commitment to promoting women as part of his "Abenomics" strategy to revive the economy.